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Acute Renal Failure
Definition
MDRDeGFR= 186 x Screatˉ sup1sup1⁵⁴ X Age ˉ⁰sup2degsup3 X 121 [if black] X
o74 [if female] Undersetimates GFR in healthy people (when GFR gt60
mlmin)
Cockcroft-Gault formula(140-Age) X Mass (In KG) X [o85 if female]72 X Serum Creat
The non-steady-state conditions that prevail in ARF preclude estimation of GFR using standard formulae derived from patients with chronic kidney disease
RR= 24
RR= 415
RR=637
Shortcomings
The assignement of corresponding changes in serum creat and changes in urine output to the same strata is not based on evidence The criteria that results in the least favorable rifle strata to be used
The patient would progress from risk on day one to injury on day two and failure on day three even though the actual GFR has been lt10 mLmin over the entire period
It is impossible to calculate the change in serum creatinine in patients who present with ARF but without a baseline measurement of the serum creat The authors of the RIFLE criteria suggest back-calculating an estimated baseline creat using the four-variable MDRD equation assuming a baseline GFR of 75 mLmin per 173 m2
Diagnostic criteria
Abrupt (within 48 hours) absolute increase in the serum creatinine concentration of ge 03 mgdL (264 micromolL) from baseline
Or a percentage increase in the serum creatinine concentration of ge 50 percent
Or oliguria of less than 05 mLkg per hour for more than six hours bullThe diagnostic criteria could be applied only after volume status had been optimized bullUrinary tract obstruction needed to be excluded if oliguria was used as the sole diagnostic criteria
Syndromes of acute renal failurePrerenal ARF Intravascular volume depletion Decreased effective blood volume Altered intrarenal hemodynamics preglomerular (afferent) vasoconstriction postglomerular (efferent) vasodilation
Intrinsic ARF Acute tubular necrosis ischemic nephrotoxic acute interstitial nephritis acute glomerulonephritis acute vascular syndromes
Postrenal ARF
Epidemiology of ARF
The observed incidence etiology and outcomes of ARF are highly dependent upon the populations studied and the definition of ARF employed
The absence of centralized registries to track the incidence and outcomes of patients with ARF has hindered our understanding of its epidemiology
NATURE CLINICAL PRACTICE NEPHROLOGY (2006) 2364-377
The changing epidemiology of acute renal failure
Non -ICU ICU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Definition
MDRDeGFR= 186 x Screatˉ sup1sup1⁵⁴ X Age ˉ⁰sup2degsup3 X 121 [if black] X
o74 [if female] Undersetimates GFR in healthy people (when GFR gt60
mlmin)
Cockcroft-Gault formula(140-Age) X Mass (In KG) X [o85 if female]72 X Serum Creat
The non-steady-state conditions that prevail in ARF preclude estimation of GFR using standard formulae derived from patients with chronic kidney disease
RR= 24
RR= 415
RR=637
Shortcomings
The assignement of corresponding changes in serum creat and changes in urine output to the same strata is not based on evidence The criteria that results in the least favorable rifle strata to be used
The patient would progress from risk on day one to injury on day two and failure on day three even though the actual GFR has been lt10 mLmin over the entire period
It is impossible to calculate the change in serum creatinine in patients who present with ARF but without a baseline measurement of the serum creat The authors of the RIFLE criteria suggest back-calculating an estimated baseline creat using the four-variable MDRD equation assuming a baseline GFR of 75 mLmin per 173 m2
Diagnostic criteria
Abrupt (within 48 hours) absolute increase in the serum creatinine concentration of ge 03 mgdL (264 micromolL) from baseline
Or a percentage increase in the serum creatinine concentration of ge 50 percent
Or oliguria of less than 05 mLkg per hour for more than six hours bullThe diagnostic criteria could be applied only after volume status had been optimized bullUrinary tract obstruction needed to be excluded if oliguria was used as the sole diagnostic criteria
Syndromes of acute renal failurePrerenal ARF Intravascular volume depletion Decreased effective blood volume Altered intrarenal hemodynamics preglomerular (afferent) vasoconstriction postglomerular (efferent) vasodilation
Intrinsic ARF Acute tubular necrosis ischemic nephrotoxic acute interstitial nephritis acute glomerulonephritis acute vascular syndromes
Postrenal ARF
Epidemiology of ARF
The observed incidence etiology and outcomes of ARF are highly dependent upon the populations studied and the definition of ARF employed
The absence of centralized registries to track the incidence and outcomes of patients with ARF has hindered our understanding of its epidemiology
NATURE CLINICAL PRACTICE NEPHROLOGY (2006) 2364-377
The changing epidemiology of acute renal failure
Non -ICU ICU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
MDRDeGFR= 186 x Screatˉ sup1sup1⁵⁴ X Age ˉ⁰sup2degsup3 X 121 [if black] X
o74 [if female] Undersetimates GFR in healthy people (when GFR gt60
mlmin)
Cockcroft-Gault formula(140-Age) X Mass (In KG) X [o85 if female]72 X Serum Creat
The non-steady-state conditions that prevail in ARF preclude estimation of GFR using standard formulae derived from patients with chronic kidney disease
RR= 24
RR= 415
RR=637
Shortcomings
The assignement of corresponding changes in serum creat and changes in urine output to the same strata is not based on evidence The criteria that results in the least favorable rifle strata to be used
The patient would progress from risk on day one to injury on day two and failure on day three even though the actual GFR has been lt10 mLmin over the entire period
It is impossible to calculate the change in serum creatinine in patients who present with ARF but without a baseline measurement of the serum creat The authors of the RIFLE criteria suggest back-calculating an estimated baseline creat using the four-variable MDRD equation assuming a baseline GFR of 75 mLmin per 173 m2
Diagnostic criteria
Abrupt (within 48 hours) absolute increase in the serum creatinine concentration of ge 03 mgdL (264 micromolL) from baseline
Or a percentage increase in the serum creatinine concentration of ge 50 percent
Or oliguria of less than 05 mLkg per hour for more than six hours bullThe diagnostic criteria could be applied only after volume status had been optimized bullUrinary tract obstruction needed to be excluded if oliguria was used as the sole diagnostic criteria
Syndromes of acute renal failurePrerenal ARF Intravascular volume depletion Decreased effective blood volume Altered intrarenal hemodynamics preglomerular (afferent) vasoconstriction postglomerular (efferent) vasodilation
Intrinsic ARF Acute tubular necrosis ischemic nephrotoxic acute interstitial nephritis acute glomerulonephritis acute vascular syndromes
Postrenal ARF
Epidemiology of ARF
The observed incidence etiology and outcomes of ARF are highly dependent upon the populations studied and the definition of ARF employed
The absence of centralized registries to track the incidence and outcomes of patients with ARF has hindered our understanding of its epidemiology
NATURE CLINICAL PRACTICE NEPHROLOGY (2006) 2364-377
The changing epidemiology of acute renal failure
Non -ICU ICU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
RR= 24
RR= 415
RR=637
Shortcomings
The assignement of corresponding changes in serum creat and changes in urine output to the same strata is not based on evidence The criteria that results in the least favorable rifle strata to be used
The patient would progress from risk on day one to injury on day two and failure on day three even though the actual GFR has been lt10 mLmin over the entire period
It is impossible to calculate the change in serum creatinine in patients who present with ARF but without a baseline measurement of the serum creat The authors of the RIFLE criteria suggest back-calculating an estimated baseline creat using the four-variable MDRD equation assuming a baseline GFR of 75 mLmin per 173 m2
Diagnostic criteria
Abrupt (within 48 hours) absolute increase in the serum creatinine concentration of ge 03 mgdL (264 micromolL) from baseline
Or a percentage increase in the serum creatinine concentration of ge 50 percent
Or oliguria of less than 05 mLkg per hour for more than six hours bullThe diagnostic criteria could be applied only after volume status had been optimized bullUrinary tract obstruction needed to be excluded if oliguria was used as the sole diagnostic criteria
Syndromes of acute renal failurePrerenal ARF Intravascular volume depletion Decreased effective blood volume Altered intrarenal hemodynamics preglomerular (afferent) vasoconstriction postglomerular (efferent) vasodilation
Intrinsic ARF Acute tubular necrosis ischemic nephrotoxic acute interstitial nephritis acute glomerulonephritis acute vascular syndromes
Postrenal ARF
Epidemiology of ARF
The observed incidence etiology and outcomes of ARF are highly dependent upon the populations studied and the definition of ARF employed
The absence of centralized registries to track the incidence and outcomes of patients with ARF has hindered our understanding of its epidemiology
NATURE CLINICAL PRACTICE NEPHROLOGY (2006) 2364-377
The changing epidemiology of acute renal failure
Non -ICU ICU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Shortcomings
The assignement of corresponding changes in serum creat and changes in urine output to the same strata is not based on evidence The criteria that results in the least favorable rifle strata to be used
The patient would progress from risk on day one to injury on day two and failure on day three even though the actual GFR has been lt10 mLmin over the entire period
It is impossible to calculate the change in serum creatinine in patients who present with ARF but without a baseline measurement of the serum creat The authors of the RIFLE criteria suggest back-calculating an estimated baseline creat using the four-variable MDRD equation assuming a baseline GFR of 75 mLmin per 173 m2
Diagnostic criteria
Abrupt (within 48 hours) absolute increase in the serum creatinine concentration of ge 03 mgdL (264 micromolL) from baseline
Or a percentage increase in the serum creatinine concentration of ge 50 percent
Or oliguria of less than 05 mLkg per hour for more than six hours bullThe diagnostic criteria could be applied only after volume status had been optimized bullUrinary tract obstruction needed to be excluded if oliguria was used as the sole diagnostic criteria
Syndromes of acute renal failurePrerenal ARF Intravascular volume depletion Decreased effective blood volume Altered intrarenal hemodynamics preglomerular (afferent) vasoconstriction postglomerular (efferent) vasodilation
Intrinsic ARF Acute tubular necrosis ischemic nephrotoxic acute interstitial nephritis acute glomerulonephritis acute vascular syndromes
Postrenal ARF
Epidemiology of ARF
The observed incidence etiology and outcomes of ARF are highly dependent upon the populations studied and the definition of ARF employed
The absence of centralized registries to track the incidence and outcomes of patients with ARF has hindered our understanding of its epidemiology
NATURE CLINICAL PRACTICE NEPHROLOGY (2006) 2364-377
The changing epidemiology of acute renal failure
Non -ICU ICU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Diagnostic criteria
Abrupt (within 48 hours) absolute increase in the serum creatinine concentration of ge 03 mgdL (264 micromolL) from baseline
Or a percentage increase in the serum creatinine concentration of ge 50 percent
Or oliguria of less than 05 mLkg per hour for more than six hours bullThe diagnostic criteria could be applied only after volume status had been optimized bullUrinary tract obstruction needed to be excluded if oliguria was used as the sole diagnostic criteria
Syndromes of acute renal failurePrerenal ARF Intravascular volume depletion Decreased effective blood volume Altered intrarenal hemodynamics preglomerular (afferent) vasoconstriction postglomerular (efferent) vasodilation
Intrinsic ARF Acute tubular necrosis ischemic nephrotoxic acute interstitial nephritis acute glomerulonephritis acute vascular syndromes
Postrenal ARF
Epidemiology of ARF
The observed incidence etiology and outcomes of ARF are highly dependent upon the populations studied and the definition of ARF employed
The absence of centralized registries to track the incidence and outcomes of patients with ARF has hindered our understanding of its epidemiology
NATURE CLINICAL PRACTICE NEPHROLOGY (2006) 2364-377
The changing epidemiology of acute renal failure
Non -ICU ICU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Syndromes of acute renal failurePrerenal ARF Intravascular volume depletion Decreased effective blood volume Altered intrarenal hemodynamics preglomerular (afferent) vasoconstriction postglomerular (efferent) vasodilation
Intrinsic ARF Acute tubular necrosis ischemic nephrotoxic acute interstitial nephritis acute glomerulonephritis acute vascular syndromes
Postrenal ARF
Epidemiology of ARF
The observed incidence etiology and outcomes of ARF are highly dependent upon the populations studied and the definition of ARF employed
The absence of centralized registries to track the incidence and outcomes of patients with ARF has hindered our understanding of its epidemiology
NATURE CLINICAL PRACTICE NEPHROLOGY (2006) 2364-377
The changing epidemiology of acute renal failure
Non -ICU ICU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Epidemiology of ARF
The observed incidence etiology and outcomes of ARF are highly dependent upon the populations studied and the definition of ARF employed
The absence of centralized registries to track the incidence and outcomes of patients with ARF has hindered our understanding of its epidemiology
NATURE CLINICAL PRACTICE NEPHROLOGY (2006) 2364-377
The changing epidemiology of acute renal failure
Non -ICU ICU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
The observed incidence etiology and outcomes of ARF are highly dependent upon the populations studied and the definition of ARF employed
The absence of centralized registries to track the incidence and outcomes of patients with ARF has hindered our understanding of its epidemiology
NATURE CLINICAL PRACTICE NEPHROLOGY (2006) 2364-377
The changing epidemiology of acute renal failure
Non -ICU ICU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
NATURE CLINICAL PRACTICE NEPHROLOGY (2006) 2364-377
The changing epidemiology of acute renal failure
Non -ICU ICU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Non -ICU ICU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Key Points
The absolute incidence of acute renal failure (ARF) has increased in the past two decades while the mortality rate has remained relatively static
The lack of a standard definition of ARF complicates the process of identifying the factors that underlie changes in epidemiology of this condition
Despite the use of different definitions in different studies various factors that have contributed to altered epidemiology of ARF in the past few decades have been identified
These factors include geographical site of disease onset (developed vs developing countries community vs hospital vs intensive care unit) patient age infections (HIV malaria leptospirosis and hantavirus) concomitant illnesses (cardiopulmonary failure hematooncological disease) and interventions (hematopoietic progenitor cell and solid organ transplantation)
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Prerenal Acute Renal Failure
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
GFR is reduced as a result of hemodynamic disturbances that decrease glomerular perfusion
The defining feature of prerenal ARF is the absence of cellular injury and the normalization of renal function with reversal of the altered hemodynamic factors
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
OF PRERENAL ARF
Pathophsiology
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Diagnosis of Prerenal ARF
HxPEUrine sediment (usually normal without cellular
elements or abnormal casts unless chronic kidney disease is present)
UNalt 15 meqL (gt20 in ATN)UPcreatgt 20 (lt15 in ATN)FeNa lt1 (gt1 in ATN)UNaK lt14 BUNcreat gt20
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
BUNCREAT of gt20 is typical BUT is not specific to prerenal ARF and may also be seen
Obstructive uropathy Gastrointestinal bleeding Other states associated with increased urea
production
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
FE Urea
Patients on diureticsPrerenal azotemia due to vomiting on NG
suctioningFE Na may be low is sepsis RCN
myoglobinuria nonoliguric ATN acute GN urinary tract obstruction and renal allograft rejection
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Significance of the fractional excretion of urea in thedifferential diagnosis of acute renal failure
102 patients were divided into three groupsPrerenal azotemia (N 50)Prerenal azotemia treated with diuretics (N 27)ATN (N 25)
Kidney International Vol 62 (2002) pp 2223ndash2229
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups
FEUN was essentially identical in the two pre-renal groups (279 24 vs 245 23) and very different from the FEUN found in ATN (586 36 P lt 00001)
92 of the patients with prerenal azotemia had FENa lt1
48 of those patients with prerenal and diuretic therapy had FENa lt1
89 of patients with prerenal azotemia and on diuretics had a FEUNlt 35
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
FE UREA
Low FE urea lt=35 is a more sensitive and specific index than FE Na in differentiating between ARF due to prerenal azotemia and that due to ATN especially if diuretics have been administered
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
ARF Associated with ACE Inhibitors and Angiotensin
Receptor Blockers
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Acute renal failure can develop acutely when ACEI or ARB therapy is initiated or in patients receiving chronic therapy especially in patients with underlying CHF
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Predisposing factorsbull Advanced cardiac failure with low mean arterial
pressurebull Volume depletion due to diuretic therapybull The presence of renal vascular diseasebull The concomitant use agents with vasoconstrictor
effects (NSAIDs cyclooxygenase-2 inhibitors cyclosporine and tacrolimus)
bull CKD The risk of ARF is higher in patients with chronic kidney disease of any cause than in patients with normal renal function
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Serum creatinine and electrolyte concentrations should be measured before and 1 wk after initiating or changing the dose of therapy
An increase in serum creatinine of gt05 mgdl if the initial serum creatinine is lt20 mgdl or a rise of gt10 mgdl if the baseline serum creatinine is gt20 mgdl has been suggested as a threshold for discontinuation of therapy
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
The development of ARF should prompt an evaluation for cardiac failure hypotension volume depletion use of a concomitant vasoconstrictive agent or renovascular disease
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Acute Renal Failure Associated with NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Nonsteroidal anti-inflammatory drugs (NSAID) agents inhibit the synthesis of vasodilatory prostaglandins in the kidney
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Risk factors
Severe CHF Advanced liver disease Severe atherosclerotic vascular disease CKD
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Elderly patients are at increased risk due to the increased prevalence of cardiac dysfunction occult renal vascular disease and subclinical chronic kidney disease
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Abdominal Compartment Syndrome
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Unusual cause of decreased renal perfusion associated with increased intra-abdominal pressure
bull Trauma patients who require massive volume resuscitation
bull Mechanical limitations of the abdominal wall (tight surgical closures or scarring after burn injuries)
bull Medical etiologies that are characterized by intraabdominal inflammation with fluid sequestration such as bowel obstruction pancreatitis and peritonitis
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Clinical manifestationsRespiratory compromise Decreased cardiac output Intestinal ischemia Hepatic dysfunction Oliguric renal failure
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
The renal insufficiency results from decreased renal perfusion and correlates with the severity of the increased intraabdominal pressure
Oliguria develops when the intraabdominal pressure exceeds 15 mmHg with anuria developing at pressures gt30 mmHg
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Diagnosis
The diagnosis should be suspected in patients with a tensely distended abdomen and progressive oliguria
Measurement of intraabdominal bladder pressure
Abdominal compartment syndrome can be excluded when the bladder pressure is lt10 mmHg and is virtually always present if the pressure is gt25 mmHg
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Treatment
Abdominal decompressionParacentesis if massive ascitesSurgical decompression is required in the
majority of patientsRenal failure usually recovers promptly
after relief of the increased intraabdominal pressure
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Postrenal Acute Renal Failure
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Intrinsic
Extrinsic
Lower tract obstruction
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Urine output
The obstruction Complete Anuria
InComplete
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Pathophysiology
After the acute onset of obstruction GFR declines progressively but it does not fall to zero
Factors that maintain GFR include continued salt and water reabsorption along the nephron dilatation of the collecting system and alterations in renal hemodynamics
Intratubular pressure rises acutely but it begins to decline within the first 4 to 8 h returning to nearly normal by 24 h
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Ureteral Pr
RBF GFR
1- 2 H
2-5 H
Late phase
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Complete obstruction
Recovery after relief of obstruction depends on
Severity Duration
bull Less than 1 wk duration recovery completebull Little or no recovery after 12 wk
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Partial obstruction
The course after relief of partial obstruction is less predictable
Depends on Severity Duration Presence of infection or preexisting renal disease
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Relief of obstruction may be accompanied by a post-obstructive diuresis
Excretion of salt and water retained during the obstruction
Persistent salt-wasting and impaired urinary concentrating ability
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Diagnosis
Elderly male patientsMeasurement of a post-voiding residual
bladder volume either by an bedside ultrasound bladder scan or by placement of an indwelling bladder catheter
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Diagnosis
Ultrasonography Sensitivity and specificity are highNon diagnostic
Early in the course of postrenal ARF Severe volume depletion Obstruction is due to retroperitoneal disease (eg
retroperitoneal fibrosis tumors adenopathy) encasing the ureter and preventing dilatation
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Diagnosis
Computed tomography
Non-contrasted CT scanning may be particularly useful for the identification of obstructing kidney stones
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Intrinsic ARF
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Etiology of Intrinsic ARF
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Acute tubular necrosis
Ischemic
hypotension hypovolemic shock sepsis cardiopulmonary arrest cardiopulmonary bypass Nephrotoxic
drug-induced aminoglycosides radiocontrast agents amphotericin cisplatinum acetaminophen pigment nephropathy intravascular hemolysis rhabdomyolysis
Acute interstitial nephritis Dug-induced penicillins cephalosporins sulfonamides rifampin dilantin furosemide non-steroidal antiinflammatory drugs Infection-related bacterial infection viral infections rickettsial disease tuberculosis
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Systemic diseases
systemic lupus erythematosus sarcoidosis
Sjoumlgren syndrome
tubulointerstitial nephritis and uveitis (TINU) syndrome
Malignancy
malignant infiltration of interstitium multiple myeloma
Idiopathic
Acute glomerulonephritis
poststreptococcal glomerulonephritis postinfectious glomerulonephritis
endocarditis-associated glomerulonephritis systemic vasculitis
hemolytic uremic syndromethrombotic thrombocytopenic purpura rapidly progressive glomerulonephritis (RPGN)Acute vascular syndromes
renal artery thromboembolism
renal artery dissection
renal vein thrombosis
atheroembolic disease
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
ATN
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Acute tubular necrosis is the most common form of intrinsic ARF (85 )
Tubular injury Nephrotoxic (35) Ischemic (50) Multifactorial
Profound ischemic injury may result in bilateral cortical necrosis
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Nephrotoxic ATN
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Clinical course
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Pathogenesis of ATN
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Recovery from Ischemic Injury
In contrast to the heart and brain where ischemic injury results in permanent cell loss the kidney is able to completely restore its structure and function after acute ischemic or toxic injury
The recovery from tubular necrosis involves the dedifferentiation and proliferation of remaining viable tubular epithelial cells followed by reestablishment of cellular polarity normal histologic appearance and physiologic function
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Under normal circumstances renal tubular cells in vivo are quiescent and do not divide in response to growth factors
After ischemic or toxic injury alterations in gene expression are observed that are similar to those induced in vitro by growth factors
Multiple growth factors including (IGF-1) (EGF) and (HGF) and their receptors are upregulated during the regenerative process after renal injury
Administration of exogenous IGF-1 EGF or HGF to experimental animals after ischemic or toxic renal injury accelerates renal regeneration
Concern has been raised that growth factors may also have a deleterious effect augmenting tubulointerstitial injury and fibrosis
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Short-term Outcomes
The outcome of ATN is highly dependent on the severity of comorbid conditions
Uncomplicated ATN is associated with mortality rates of 7 to 23
Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80
Mortality rates increases with the number of failed organ systems
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Long-term Outcomes
Long term outcomes in ARF in patients treated with continuous RRT Am J Kidney Dis 2002
Long-term outcomes of patients who survive are good
Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN) in-hospital mortality was 69
Patients who survived to hospital discharge 6-mo survival was 77 1-yr survival was 69 and 5-yr survival was 50
59 of surviving patients had no residual renal insufficiency and only 10 required chronic dialysis therapy
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Radiocontratst Nephropathy
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Contrast media induced nephropathy (CMIN) is the third highest cause of hospital-acquired acute renal failure
In nearly half of these patients CMIN occurred during cardiac diagnostic or interventional procedures such as percutaneous coronary intervention
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
ARFincrease in serum creat ofgt50 above baseline or gt1 mgdl if baselinegt2 mgdl
Normal baseline creat negilgible risk Mild to moderate CKD 5-10 risk
Mild to moderate CKD + DM 10- 40
Advanced renal insufficiency gt50 risk
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Pathogenesis
Haemodynamic alterations and tubuloglomerular feedback
The injection of CM induces early rapid renal vasodilatation followed by prolonged vasoconstriction with an increase in intrarenal vascular resistances a reduction of total renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR)
Conversely the effect on the extrarenal vasculature is transient vasoconstriction that precedes a stable decrease in vascular peripheral resistances
The resulting renal ischaemia due to these haemodynamic effects is in part responsible for nephropathy
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Endothelial dysfunctionVasoactive mediatorsFree radicals and reperfusion damageHaemorheological factorsTubular toxicity and immunological
mechanisms
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Treatment
The best treatment of contrast-induced renal failure is prevention
The use if clinically possible of ultrasonography magnetic resonance imaging or CT scanning without radiocontrast agents particularly in high-risk patients
The use of lower doses of contrast and avoidance of repetitive studies that are closely spaced (within 48 to 72 hours)
Avoidance of volume depletion or nonsteroidal antiinflammatory drugs both of which can increase renal vasoconstriction
The use of low or iso-osmolal nonionic contrast agents
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Treatment
The administration of Intravenous SalineIsotonic saline at a rate of 1 mLkg per hour
begun at least two and preferably 6 to 12 hours prior to the procedure and continuing for 6 to 12 hours after contrast administration
The administration of the antioxidant Acetylcysteine
Dose of 600 to 1200 mg orally twice daily administered the day before and the day of the procedure based upon its potential for benefit and low toxicity and cost
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Treatment
Routine hemofiltration or hemodialysis for the prevention of contrast nephropathy in patients with stage 3 and 4 CKD is not recommended
More data are needed in stage 5 CKD (Prophylactic use of hemodialysis in patients with stage 5 CKD can be consideredprovided that a functioning access is already available)
Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy a systematic review Am J Kidney Dis 2006 48361
Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis A randomized controlled trial J Am Coll Cardiol 2007 501015
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Treatment
There is no indication for prophylactic dialysis for the prevention of volume overload in dialysis-dependent patients
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Treatment
Therapies with Limited EvidenceCalcium Channel BlockersDiureticsAtrial Natriuretic Peptide (ANP)Endothelin (ET) AntagonistsProstaglandin E1ACE Inhibitors
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
The high-osmolal contrast media (osmolality 1500ndash1800 mOsmkg) are first generation agents
Low-osmolal contrast media still have an increased osmolality compared with plasma (600ndash850 mOsmkg)
The newest nonionic radiocontrast agents have a lower osmolality 290 mOsmkg iso-osmolal to plasma
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
In high-risk patient populations (patientswith underlying renal insufficiency and diabetes) both low-osmolar and iso-osmolar contrasts tend to reduce the risk of contrast nephropathy as compared to the high-osmolar compounds
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
The volume of contrast administered to the patien also appears to correlate with the incidence of nephrotoxicity
In patients who undergo only diagnostic coronary procedures the volume of dye (approximately 100 mL) is considerably less than in patients who undergo interventional procedures (approximately 250-300 mL)
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Heme pigment-induced acute tubular necrosis
Myoglobinuria rhabdomyolysis
Hemoglobinuria intravascular hemolysis
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Rhabdomyolysis
The release of muscle cell contents as the result of traumatic or nontraumatic injury of skeletal muscle
Physical findings may consist of bull Tender ldquodoughyrdquo muscles bull Edemabull weakness bull Compartmental compression symptoms with signs and
symptoms of neurovascular compromise may develop necessitating the need for emergent fasciotomy
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
The majority of cases of rhabdomyolysis are nontraumatic
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Laboratory abnormalities
Hypovolemia and High AG acidosis
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
The urine may have a low FENa despite tubular injury
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria
Heme-pigmented granular castsPlasma is normal color in myoglobinuria
and red brown in hemoglobinuria
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Treatment
IVFIsotonic saline at 1 to 2 liters per hourFluids are titrated to maintain a urine output
of 200 to 300 mLhourContinue until the urine discoloration clears
and plasma creatine kinase decreases to less than 5000 to 10000 UL (or there is cessation of hemolysis) or symptomatic fluid overload develops
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Treatment
Alkalinization
Mannitol diuresis
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Acute Interstitial Nephritis
Acute interstitial nephritis (AIN) is a syndrome of ARF associated with an inflammatory infiltrate involving the renal interstitium
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Drug hypersensitivity
PenicillinCephalosporinSulfonamideFluoroquinoloneRifampin
NSAIDsPhenytoinFurosemideThiazide diureticsAllopurinolAlpha interferonCimetidineOmeprazole
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Others
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Methicillin induced AIN
Renal symptoms typically develop 2 to 3 weeks after the initiation of treatmentbull Hematuriabull Pyuria with white blood cell castsbull Proteinuria lt 1gd (can be nephrotic with
NSAIDs)bull Renal failure in 50 of patients
Extrarenal manifestationsbull Fever in 80 bull Eosinophilia in 80 bull Rash in 25
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Other kinetics
Within 2 to 3 days after rechallenge with a drug with previous sensitisation
De novo in response to a med previoulsy tolerated medication
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Renal failure is the most prominent featureDevelops within 3 wk of initiation of drug
therapy in 80Hematuria and pyuria each are present in
only 50 of patients Extrarenal manifestations including fever
maculo-papular rash arthralgias and eosinophilia are each present in fewer than 50
All of them together in lt5
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Eosinophiluria Diagnostic value is poor
Other conditions associated with Eosinophiluria
Prostatitis RPGN Bladder Cancer Renal Atheroembolic disease
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Eosinophiluria
PPV for AIN of only 50
NPV of 90
Thus the presence of eosinophiluria is not strongly predictive of a diagnosis of AIN however its absence is useful in excluding the diagnosis
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Renal biopsy
Failure to improve after discontinuation of potential offending drug
If the potential offending drug is critical for therapy
If immunosupressive therapy is considered
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
SupportiveDicontinue offending drugPrednisone 1mgkgd for 4 weeksControversialRcommended if biopsy proven AIN and who have persistent
renal failure 1 week after DC the offending medication
adjunct cyclophosphamide
Treatment
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Hepatorenal syndrome
ARF in HRS results from profound renal vasoconstriction in the setting of histologically normal kidneys
Although many of the features of HRS resemble prerenal azotemia the defining feature is a lack of improvement in renal function with volume expansion
Recovery of renal function is usually observed after restoration of hepatic function after liver transplantation
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Diagnostic criteria
Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
A plasma creatinine concentration above 15 mgdL (133 micromolL) that progresses over days to weeks
The absence of any other apparent cause for the renal disease including shock ongoing bacterial infection current or recent treatment with nephrotoxic drugs and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease
Urine red cell excretion of less than 50 cellsHPF and protein excretion less than 500 mgday
Lack of improvement in renal function after volume expansion with intravenous albumin (1 gkg of body weight per day up to 100 gday) for at least two days and withdrawal of diuretics
Urine Nalt10
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Treatment
Management of underlying causeStop diureticsLow salt diet and free water restriction if
hyponatremiaMidodrine + Octreotide + AlbuminTerlipressin + AlbuminRRTTIPS
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
The management of patients with acute renal failure or acute kidney injury (AKI) is principally supportive with renal replacement therapy (RRT) indicated in patients with severe kidney injury
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Treatment of ARF
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Prevention
Renal hypoperfusion is a predisposing factor to the development of renal failure
Optimizing vascular hemodynamics to ensure adequate renal perfusion is a fundamental principle in avoiding renal failure
Avoidance or discontinuation of drugs that increase renal vaso-constriction such as NSAID and selective COX-2 inhibitors
Potentially nephrotoxic medications should be avoided particularly in high-risk patients whenever possible
Using alternative imaging techniques such as MRI scanning should be considered in patients at high risk for contrast
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Pharmacologic Treatment of Acute Renal Failure
DopamineLoop diureticsANPThyroxineIGF-1
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Indications for RRT
Refractory fluid overload Hyperkalemia (plasma potassium
concentration gt65 meqL) or rapidly rising potassium levels
Metabolic acidosis (pH less than 71) Signs of uremia such as pericarditis
neuropathy or an otherwise unexplained decline in mental status
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Timing of initiation of RRT
It is not possible to specify a specific duration of renal injury or level of azotemia at which RRT should be optimally initiated
It is unproven whether initiation of earlier or prophylactic dialysis offers any clinical or survival benefit
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
The optimal timing for initiation of RRT in patients with AKI will require an adequately powered prospective randomized trial
Adequate design of such a trial is limited by the current inability to quickly prospectively identify patients with early AKI who will have protracted renal injury and eventually require RRT
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Initiation of dialysis prior to the development of symptoms and signs of renal failure due to AKI is recommended
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Current data do not support the superiority of either CRRT or IHD
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
Learning objectives
Understanding the limitations of serum creatFormulation of a DDxUnderstanding of the pathophysiology of ARFPrevention of ARF
THANK YOU
THANK YOU
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