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1Kamran fazel MD, FCCM Slide 2 Slide 3 HISTORY DEFINITION EPIDEMIOLOGY ETIOLOGY SUBTYPE PROGNOSIS BIOMARKER RISK FACTOR EVALUATION MANAGEMENT&GUIDELINE Slide 4 1 -HISTORY Slide 5 Acute Kidney Injury 2 nd Century AD: Galen surmises urine formed from kidneys 330-1453 AD: Byzantine physicians describe oliguria as symptom of AKI, as well as detailed urine findings in AKI; also, the transition to polyuric phase as late finding in AKI is recognized 330-1453 AD: likely precursors to ATN described: Aetius: ..the reasons for the destruction of the kidney are the toxic influence of remedies and poisons, and external pressure Nonus: hematuria results from poisonous drugs and serpent venom (Eftychiadis AC, Am J Nephrol 1997) Slide 6 Acute Kidney Injury 1827: English physician Richard Bright describes microscopic hematuria, oliguria, and edema in acute and chronic renal inflammatory states, gives eponymic definition for.acute/chronic GN Slide 7 Acute Kidney Injury WWI & WWII: Post-traumatic oliguria seen in combatants, crush syndrome evolves as an AKI dx 1950-1960s: AKI found retrospectively in ~20% of post-op open heart/aortic surgery Slide 8 Acute Kidney Injury WW I: observations of thirst and oliguria in combat victims led to relationship between blunt trauma and AKI (Better, OS 1997) WWII: Spanish surgeon Joseph Trueta observes same in Spanish Civil War, WWII combatants Induces renal cortical vasospasm experimentally (Trueta, et al., 1947) WWII: Bywaters and Beall link myoglobin to AKI in crush syndrome during London Blitz (1940) Slide 9 2-Definition of AKI Slide 10 UK Renal Association 5th Edition, 2011 Acute kidney injury (AKI) has now replaced the term acute renal failure and an universal definition and staging system has been proposed to allow earlier detection and management of AKI. The new terminology enables healthcare professionals to consider the disease as a spectrum of injury. This spectrum extends from less severe forms of injury to more advanced injury when acute kidney failure may require renal replacement therapy (RRT) Slide 11 Clinically AKI is characterised by a rapid reduction in kidney function resulting in a failure to maintain fluid, electrolyte and acid-base homoeostasis. Slide 12 There are more than 35 definitions of AKI (formerly acute renal failure) in literature! Mehta R, Chertow G: Acute renal failure definitions and classification: Time for change? Journal of American Society of Nephrology 2003; 14:2178-2187. Slide 13 Acute Kidney Injury 2001 : Acute Dialysis Quality Initiative (ADQI) Risk: 1.5x inc in SCr, GFR dec 25%, UOP Modification of the RIFLE classification by Acute Kidney Injury Network (AKIN). Recognizes that small changes in serum creatinine (>0.3 mg/dl) adversely impact clinical outcome. Uses serum creatinine, urinary output and time. Coca S, Peixoto A, Garg A, et al.: The prognostic importance of a small acute decrement in kidney function in hospitalized patients: a systematic review and meta-analysis. American Journal of Kidney Diseases 2007; 50:712- 720. Slide 18 AKIN stage Serum Creatinine Criteria Urinary Output Criteria Time 1 Cr 0.3 mg/dL or 150-200% from baseline < 0.5 mL/kg/hr > 6 hrs 2 Cr to > 200-300% from baseline < 0.5 mL/kg/hr > 12 hrs 3 Cr to > 300% from baseline or Cr 4mg/dL with an acute rise of at least 0.5 mg/dL < 0.5 mL/kg/hr or anuria X 24 hrs X 12 hrs * Patients needing RRT are classified stage 3 despite the stage they were before starting RRT Mehta R, Kellum J, Shah S, et al.: Acute kidney Injury Network: Report of an Initiative to improve outcomes in Acute Kidney Injury. Critical Care 2007; 11: R31. Slide 19 3-Epidemiology Slide 20 AKI occurs in 7% of hospitalized patients. 36 67% of critically ill patients (depending on the definition). 5-6% of ICU patients with AKI require RRT. Nash K, Hafeez A, Hou S: Hospital-acquired renal insufficiency. American Journal of Kidney Diseases 2002; 39:930-936. Hoste E, Clermont G, Kersten A, et al.: RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: A cohort analysis. Critical Care 2006; 10:R73. Osterman M, Chang R: Acute Kidney Injury in the Intensive Care Unit according to RIFLE. Critical Care Medicine 2007; 35:1837-1843. Slide 21 Data from the Intensive Care National Audit Research Centre (ICNARC) suggests that AKI accounts for nearly 10 percent of all.ICU bed days Slide 22 4-Etiology Slide 23 Etiology Hemodynamic 30% Parenchymal 65% Acute tubular necrosis 55% Acute glomerulonephritis 5% Vasculopathy 3% Acute interstitial nephritis 2% Obstruction 5% Slide 24 Sepsis Major surgery Low cardiac output Hypovolemia Medications (20%) Uchino S, Kellum J, Bellomo R, et al.: Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 2005; 294:813-818. Slide 25 NSAIDs Aminoglycosides Amphotericin Penicillins Acyclovir Cytotoxics Radiocontrast dye Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the Intensivist. Critical Care Medicine 2010; 38:261-275. Slide 26 5-Subtype Slide 27 Subtype Acute Kidney Injury PRERENAL AKI INTRINSICPOSTRENAL Slide 28 Acute Kidney Injury PRERENAL Volume loss/Sequestration Impaired Cardiac Output Hypotension (and potentially hypo-oncotic states) Net result: glomerular hypoperfusion Slide 29 Acute Kidney Injury RENAL/INTRINSIC Vascular disorders: small vessel large vessel Glomerulonephritis Interstitial disorders: Inflammation intercalative processes Tubular necrosis: Ischemia Toxin Pigmenturia Slide 30 Acute Kidney Injury POSTRENAL Intrarenal Crystals Proteins Extrarenal Pelvis/Ureter Bladder/Urethra Slide 31 6-PROGNOSIS Slide 32 Mortality increases proportionately with increasing severity of AKI (using RIFLE). AKI requiring RRT is an independent risk factor for in- hospital mortality. Mortality in pts with AKI requiring RRT 50-70%. Even small changes in serum creatinine are associated with increased mortality. Hoste E, Clermont G, Kersten A, et al.: RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: A cohort analysis. Critical Care 2006; 10:R73. Chertow G, Levy E, Hammermeister K, et al.: Independent association between acute renal failure and mortality following cardiac surgery. American Journal of Medicine 1998; 104:343-348. Uchino S, Kellum J, Bellomo R, et al.: Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 2005; 294:813- 818. Coca S, Peixoto A, Garg A, et al.: The prognostic importance of a small acute decrement in kidney function in hospitalized patients: a systematic review and meta-analysis. American Journal of Kidney Diseases 2007; 50:712-720. Slide 33 Acute kidney injury has a poor prognosis with the mortality ranging from 10%-80% Patients who present with uncomplicated AKI, have a mortality rate of up to 10%. In contrast, patients presenting with AKI and multiorgan failure have been reported to have mortality rates of over 50%. If renal replacement therapy is required the mortality rate rises further to as high as 80% Slide 34 Non-Oliguric vs. Oliguric vs. Anuric Oliguric renal failure. Functionally, urine output less than that required to maintain solute balance (cant excrete all solute taken in). Defined as urine output < 400ml/24hr. Anuric renal failure. Defined as urine output < 100ml/24hr. Less common suggests complete obstruction, major vascular catastrophy, or more commonly severe ATN. Slide 35 Non-Oliguric vs. Oliguric vs. Anuric Classifying by urine output may help establish a cause. Oliguria more common with obstruction, prerenal azotemia Nonoliguric intrarenal causes nephrotoxic ATN, acute GN, AIN. More importantly, assists in prognosis. Significantly higher mortality with oliguric renal failure. 80% vs. 25% mortality in Oliguric vs. non-oliguric ARF Nonoliguric renal failure may also suggest greater liklihood of recovery of function. Slide 36 7-BIOMARKER Slide 37 BIOMARKER RESEARCH IN DEFINITIONS AND GOALS a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention a biomarker is any substance, structure or process that can be measured in the body or its products and influence or predict the incidence or outcome of disease Slide 38 What is GFR? How is it Calculated? The Glomerular Filtration Rate (GFR) is the volume of fluid filtered from glomerular capillaries into the Bowmans capsule per unit time Slide 39 Slow rise in Cr until eventually a new steady state is reached Large acute drop in GFR with oligoanuria Only a small early rise in Cr: not easy to recognise as AKI Suspect AKI in a sick patient with a modest rise in their creatinine GFR falls rapidly to near zero - only shown by oliguria Slide 40 Limitations to Serum Creatinine as a Reflection of GFR The serum creatinine concentration does not increase above the normal range until the GFR declines below 50 mL/min, and large declines in GFR may occur above this level without a concomitant increase in the serum.creatinine value Slide 41 Limitations to Serum Creatinine as a Reflection of GFR In a cachectic patient with very low muscle mass, creatinine generation may be so feeble that the serum creatinine level remains normal ( Risk Factors for AKI Age > 75 yrs Chronic kidney disease (CKD, eGFR < 60 mls/min/1.73m 2 ) Cardiac failure Diabetes mellitus Hypovolemia Nephrotoxic medication Atherosclerotic peripheral vascular disease Liver disease Sepsis Slide 49 Risk Factors for Ischemic Tubular Injury Volume depletion Aminoglycosides Radiocontrast NSAIDs, Cox-2 inhibitors Sepsis Rhabdomyolysis Preexisting renal disease HTN Diabetes mellitus Age > 50 Cirrhosis Slide 50 Radiocontrast-Induced Acute Renal Failure Induces renal vasoconstriction and direct cytotoxicity via oxygen free radical formation Risk factors: Renal insufficiency- Diabetes Advanced age- > 125 ml contrast Hypotension Usually non-oliguric ARF; irreversible ARF rare Slide 51 Prevention of Radiocontrast Nephropathy InterventionStrength of Evidence Clarity of Risk-Benefit Grade of Recommendation Volume expansion with normal saline GoodClearA: Intervention is always indicated and acceptable Volume expansion with sodium bicarbonate FairClearB: Intervention may be effective and is acceptable Iso-osmolar contrastFairClearB: Intervention may be effective and is acceptable TheophyllineFairUnclearC: May be considered; minimal or no relative impact N-acetylcysteineGoodUnclearC: May be considered; minimal or no relative impact HemofiltrationFairUnclearI: Insufficient evidence to recommend for or against FenoldopamGoodUnclearD: Not useful HemodialysisGoodUnclearD: Not useful Slide 52 Avoid use of intravenous contrast in high risk patients if at all possible. Use pre-procedure volume expansion using isotonic saline (?bicarbonate). NAC Avoid concomitant use of nephrotoxic medications if possible. Use low volume low- or iso-osmolar contrast Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the Intensivist. Critical Care Medicine 2010; 38:261-275. Slide 53 Recognition of underlying risk factors Diabetes CKD Age HTN Cardiac/liver dysfunction Maintenance of renal perfusion Avoidance of hyperglycemia Avoidance of nephrotoxins Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the Intensivist. Critical Care Medicine 2010; 38:261-275. Slide 54 Intravenous albumin significantly reduces the incidence of AKI and mortality in patients with cirrhosis and SBP. Albumin decreases the incidence of AKI after large volume paracentesis. Albumin and terlipressin decrease mortality in HRS. Sort P, Navasa M, Arroyo V, et al.: Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. New England Journal of Medicine 1999; 341:403-409. Gines P, Tito L, Arroyo V, et al.: Randomised comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology 1988; 94:1493-1502. Gluud L, Kjaer M, Christensen E: Terlipressin for hepatorenal syndrome. Cochrane Database Systematic Reviews 2006; CD005162. Slide 55 KDIGO Clinical Practice Guideline for Acute Kidney Injury 4.4.3: We suggest using oral NAC, together with i.v. isotonic crystalloids, in patients at increased risk of CI-AKI. 4.4.4: We suggest not using theophylline to prevent CI-AKI. 4.4.5: We recommend not using fenoldopam to prevent CI- AKI. 4.5.1: We suggest not using prophylactic intermittent hemodialysis (IHD) or hemofiltration (HF) for contrast- mediaremoval in patients at increased risk for CI-AKI. VOL 2 | SUPPLEMENT 1 | MARCH 2012 Slide 56 9-EVALUATION Slide 57 Baseline Set of Laboratories to Consider Biochemistry urea and electrolytes Hematology CBC Urinalysis (+/- microscopy, eosinophils) Urinary Biochemistry electrolytes, urea, osmolality Microbiology urine/blood culture when/if infection suspected Imaging renal ultrasound CXR, abdominal x-ray ECG Slide 58 Acute Kidney Injury LABORATORY DATA Creatinine; also BUN/Cr ratio CBC: anemia, thrombocytopenia HCO3: anion gap, lactic acid, ketones K CPK/LDH/Uric acid/liver panel Serologies: Complement ESR, RF, ANA, ANCA, AntiGBM Electrophoresis Toxicology studies Slide 59 Evaluation of Renal Failure Is the renal failure acute or chronic? laboratory values do not discriminate between acute vs. chronic oliguria supports a diagnosis of acute renal failure Clues to chronic disease Pre-existing illness DM, HTN, age, vascular disease. Uremic symptoms fatigue, nausea, anorexia, pruritis, altered taste sensation, hiccups. Small, echogenic kidneys by ultrasound. Slide 60 Diagnostic Evaluation of Renal Failure Cumulative % Correct Diagnosis Hx, PE, LabsTherapeutic Trials Renal Biopsy 100- 80- 60- 40- 20- 0- 60% 25% 15% Slide 61 Renal Biopsy-When? Exclude pre- and post-renal failure, and clinical findings are not typical for ATN Exclude pre- and post-renal failure, and clinical findings are not typical for ATN Extra-renal manifestations that suggest a systemic disorder Extra-renal manifestations that suggest a systemic disorder Heavy proteinuria Heavy proteinuria RBC casts RBC casts Slide 62 AKI Physical Exam. Assessing volume status. Is the patient intravascularly volume depleted? Neck veins JVP Peripheral edema or lack of. Orthostatic vitals. Not always straightforward. Pt. may be edematous (low albumin) or have significant right sided heart disease. Slide 63 BUN/Creatinine ratio. > 20:1 suggest prerenal or obstruction. Can be elevated by anything leading to increased urea production/absorption. GI bleed TPN Steroids Drugs Tigecycline. Creatinine in anephric state typically only rises 1mg/dl/day. If greater should be concerned for rhabdomyolysis Slide 64 AKI: Diagnostic studies-urine Urinalysis for sediment, casts Response to volume repletion with return to baseline SCr 24-72 hr c/w prerenal event Urine Na; FENa FENa (%) = UNa x SCr x 100 SNa x UCr FENa < 1%: Prerenal FENa 1-2%: Mixed FENa > 2%: ATN Hansels stain Slide 65 Classic Lab Findings in AKI CausesU Na Fe Na *Fe Urea BUN/Cr Prerenal2%>50%40>4%>15 Slide 66 Urine Patterns in Renal Disease Urinary PatternRenal Disease Hematuria with red cell casts, heavy proteinuria, or lipiduria Glomerular disease or vasculitis Granular and epithelial casts with free epithelial cells Acute Tubular Necrosis Pyuria with white cell and granular casts and no/mild proteinuria Tubular or interstitial disease or obstruction Hematuria and pyuria with no or variable casts(excluding red cell casts) Acute interstitial nephritis, glomerular disease, vasculitis, obstruction, renal infarction Pyuria aloneUsually infections, sterile pyuria suggests TB Slide 67 10-MANAGEMENT&GUIDELINE Slide 68 5 Key Steps in Evaluating Acute Renal Failure I.Obtain a thorough history and physical; review the chart in detail II.Do everything you can to accurately assess volume status III.Always order a renal ultrasound IV.Look at the urine V.Review urinary indices Slide 69 Management Importantly, manangement of AKI is varied and depends on the cause. Given no effective pharmaceutical options, management of AKI is primarily supportive. Prerenal azotemia is usually responsive to isotonic fluid repletion Managament of ATN includes discontinuation of nephrotoxic agents, optimization of hemodynamics, continued monitoring of renal function (acid/base status, electrolyte abnormalities). Postrenal causes warrant removal of the obstruction. Slide 70 Maintain renal perfusion Correct metabolic derangements Provide adequate nutrition ? Role of diuretics Slide 71 Human kidney has a compromised ability to autoregulate in AKI. Maintaining haemodynamic stability and avoiding volume depletion are a priority in AKI. Kelleher S, Robinette J, Conger J: Sympathetic nervous system in the loss of autoregulation in acute renal failure. American Journal of Physiology 1984; 246: F379-386. Slide 72 Current studies do not include patients with established AKI. The individual BP target depends on age, co- morbidities (HTN) and the current acute illness. A generally accepted target remains MAP 65. Bourgoin A, Leone M, Delmas A, et al.: Increasing mean arterial pressure in patients with septic shock: Effects on oxygen variables and renal function. Critical Care Medicine 2005; 33:780-786. Slide 73 SAFE study no statistical difference between volume resuscitation with saline or albumin in survival rates or need for RRT. Post hoc analysis albumin was associated with increased mortality in traumatic brain injury subgroup and improved survival in septic shock patients. Finfer S, Bellomo R, Boyce N, et al.: A comparison of albumin and saline for fluid resuscitation in the intensive care unit. New England Journal of Medicine 2004; 350: 2247-2256. Slide 74 There is no evidence that from a renal protection standpoint, there is a vasopressor agent of choice to improve kidney outcome. Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the Intensivist. Critical Care Medicine 2010; 38:261-275. Slide 75 KDIGO Clinical Practice Guideline for Acute Kidney Injury 3.5.1: We recommend not using low-dose dopamine to prevent or treat AKI. 3.5.2: We suggest not using fenoldopam to prevent or treat AKI. VOL 2 | SUPPLEMENT 1 | MARCH 2012 Slide 76 Renal dose dopamine doesnt reduce the incidence of AKI, the need for RRT or improve outcomes in AKI. It may worsen renal perfusion in critically ill adults with AKI. Side effects of dopamine include increased myocardial oxygen demand, increased incidence of atrial fibrillation and negative immuno-modulating effects. Lauschke A, Teichgraber U, Frei U, et al.: Low-dose dopamine worsens renal perfusion in patients with acute renal failure. Kidney 2006; 69:1669-1674. Argalious M, Motta P, Khandwala F, et al.: Renal dose dopamine is associated with the risk of new onset atrial fibrillation after cardiac surgery. Critical Care Medicine 2005; 33:1327-1332. Slide 77 KDIGO Clinical Practice Guideline for Acute Kidney Injury 3.4.1: We recommend not using diuretics to preventAKI. 3.4.2: We suggest not using diuretics to treat AKI, exceptin the management of volume overload VOL 2 | SUPPLEMENT 1 | MARCH 2012. Slide 78 Management Cont. Things to do for patients with AKI Renally dose medications Avoid nephrotoxins Monitor I/Os Serial assessment of serum creatinine Renal Replacement Therapy (i.e dialysis) is the central component of care for patients with severe AKI The generally accepted indications for renal replacement therapy in the setting of AKI include: Acidosis Electrolyte disturbance Ingestion/Intoxication Volume Overload Overt Uremia Slide 79 Acute Kidney Injury INDICATIONS FOR RENAL REPLACEMENT THERAPY Consensus generally includes: 1. Refractory volume overload 2. Severe metabolic acidosis; HCO3 may be variable, but declining level of factor; also falling pH to 7.1-7.2 3. Hyperkalemia, with levels > 6.5, or documented rapid rise refractory to medical therapy 4. Major uremic target organ manifestations i.e. pericarditis, progressive neuropathy, seizure 5. Platelet dysfunction, bleeding diasthesis 6. AKI in setting of dialyzable drug/toxin Slide 80 Guideline 8.6 AKI : Vascular access for RRT We recommend that subclavian access should be avoided in patients at risk of progressing to CKD stage 4 or 5 due to the risks of compromising future, permanent vascular access. Slide 81 Guideline 8.7 AKI : Vascular access for RRT We suggest that non-dominant arm upper limb vasculature should be preserved as a contingency for future permanent access. Slide 82 When to call nephrology Any known dialysis patient admitted Any known renal transplant patient admitted Any case of AKI where cause not clear Worsening AKI Emergency dialysis indications Suspect glomerulonephritis Slide 83