Acute Renal Failure

Acute Renal Failure

DiagnosisStaging with RIFLE Criteria

Lab evaluationClinical featuresPathophysiology

Acute Renal Failure

• Definition may depend on whom you ask– Surgeon - - low urine output– Intensivist-- severe acidemia– Nephrologist-- rising serum creatinine

• Frequency - depends on clinical setting– 1% of all admissions to hospital– 2-5% of all individuals during a hospitalization

– 4-15% during cardiopulmonary bypass– 10-30% of all admissions to ICU

Definition

• ‘…a sudden and severe decrease in the glomerular filtration rate (GFR) sufficient to cause increases in BUN and Scr (azotemia), Na/H2O retention (edema), and development of acidemia and hyperkalemia…’

• review of 27 studies showed no 2 used the same definition “chronic renal confusion”

What’s in a name?

• lack of a universally recognized definition of ARF

• 2004 consensus conference– proposed the term acute kidney injury (AKI) to reflect the entire spectrum of ARF recognizing that an acute decline in kidney function is often secondary to an injury that causes functional or structural changes in the kidneys

Newest Definition:Mehta CritCare 2007

• An abrupt (within 48 h) reduction in kidney function currently defined as:– an absolute increase in serum creatinine of either >= 0.3 mg/dl,

– or a percentage increase of >= 50 % or a reduction in UOP (documented oliguria of < 0.5 ml/kg per h for > 6)

The differential for any lab abnormality is:

• Lab error• Lab error• Lab error• Iatrogenic• Polypharmacy• Real disease• IN THIS ORDER!

Acute renal failure (ARF)

• Differential for Lab abnormality: Causes:– A rise in the BUN level can occur without renal injury, such as in GI or mucosal bleeding, steroid use, or protein loading (such as IV nutrition)

– A rise in the creatinine level can result from medications (eg, cimetidine, trimethoprim) that inhibit the kidney’s tubular secretion, or an increase in creatinine production such as seen in Rhabdomyolysis. (muscle breakdown)

– True Anuria is most commonly the result of an obstructed foley catheter, or an error in recording output. The worst cause of anuria is cortical necrosis.


• An abrupt or rapid decline in renal function

• Marked by a rise in BUN (azotemia) or serum creatinine concentration– Immediately after a kidney injury, BUN or creatinine levels may be normal• The only sign of a kidney injury may be decreased urine production

• Use RIFLE Criteria to evaluate Risk.

Acute Dialysis Quality Initiative

• RIFLE Criteria Helps risk stratify patients with renal failure.

• Increased mortality seen with increases in creatinine of 0.3 to 0.5 mg/dl (70 % increase for all pts, 300 % increase in cardiac surgery pts

RIFLE criteria

• Risk low uop for 6 hours, creat up 1.5 to 2 times baseline

• Injury creat up 2 to 3 times baseline, low uop for 12 hours

• Failure Creat up > 3 times baseline or over 4, anuria

• Loss of Function Dialysis requiring for > 4 weeks

• ESRD Dialysis requiring for > 3 months

(RIFLE Criteria for Acute Renal Failure)Bellomo R - Crit Care Clin -APR-2005; 21(2): 223-37

RIFLE estimate of Mortality

• Two studies Uchino Hoste• No renal failure 4.4 % 5.5• Risk 15% 8.8• Injury 29% 11.4• Failure 53.9% 26%• Loss of Function• ESRD

Crit Care Med 2006; 34:1913-7, Hoste CCM 2006; 10:R73

RIFLE criteria

• When markers of severity of illness are looked at excluding renal data, no difference in groups is seen.


• History and Physical examination:– Nephrotoxic drug ingestion – History of trauma or unaccustomed exertion

– Blood loss or transfusions– Congestive heart failure– Exposure to toxic substances, such as ethyl alcohol or ethylene glycol


• History and Physical examination:– Exposure to mercury vapors, lead, cadmium, or other heavy metals, which can be encountered in welders and miners

– Hypotension– Volume contraction

• Vomiting/Diarrhea/Sweating/Nursing Home

– Evidence of connective tissue disorders or autoimmune diseases

Pathophysiology

• ARF may occur in 3 clinical patterns

BUN:Cr > 20:1

BUN:Cr 10-20:1

BUN:Cr > 20:1

Pathophysiology• ARF may occur in 3 clinical patterns• Suggested by labwork:

BUN:Cr > 20:1 Pre-Renal or Post-Renal

BUN:Cr 10-20:1 Intra-Renal

BUN:Cr < 10:1 Extrinsic Production of Creatinine

or a dialysis patient.


• Patients can have:– Oliguria

• Daily urine volume of less than 400 mL/d and has a worse prognosis, except in prerenal failure

• Anuria is urine output of less than 100 mL/d and, if abrupt in onset, is suggestive of bilateral obstruction or catastrophic injury to both kidneys

– Rapid or slow rise in creatinine levels– Differences in urine solute concentrations and cellular content

Prerenal ARF

• Prerenal ARF represents the most common form of kidney injury and often leads to intrinsic ARF if it is not promptly corrected

• From any form of extreme volume loss – GI, renal (diuretics, polyuria), cutaneous (eg, burns), and internal or external hemorrhage can result in this syndrome

• Systemic vasodilation or decreased renal perfusion

• Anesthetics • Drug overdose • Heart failure• Shock (eg, sepsis, anaphylaxis)

Prerenal ARF• Afferent Arteriolar vasoconstriction leading to prerenal ARF– Hypercalcemic states– Radiocontrast agents– NSAIDs– Amphotericin– Calcineurin inhibitors– Norepinephrine– Other pressor agents– Hepatorenal syndrome

• Functional renal failure • develops from diffuse • vasoconstriction in vessels supplying the kidney.

Prerenal ARF

• Efferent arteriolar vasodilation can induce prerenal ARF in volume-depleted states in the face of :– ACE Inhibitors– ARBs

• Otherwise safely tolerated and beneficial in most patients with chronic kidney disease

• Both cause afferent and efferent dilation, but efferent more

Intrinsic ARF• Structural injury in the kidney

– Most common form is acute tubular necrosis (ATN)• Either ischemic or cytotoxic • Loss of brush borders • Flattening of the epithelium• Detachment of cells• Formation of intratubular casts• Dilatation of the lumen

– Although these changes are observed predominantly in proximal tubules, injury to the distal nephron can also be demonstrated. The distal nephron may also be subjected to obstruction by desquamated cells and cellular debris.

Intrinsic ARF

• Intrarenal vasoconstriction is the dominant mechanism for the reduced glomerular filtration rate (GFR) in patients with ATN.

• Tubular injury seems to be an important concomitant finding– Urine backflow and intratubular

obstruction (from sloughed cells and debris) = reduced net ultrafiltration.

• Stressed renal microvasculature is more sensitive to potentially vasoconstrictive drugs and otherwise tolerated changes in systemic blood pressure. – Injured kidney vasculature has an

impaired vasodilatory response and loses its autoregulatory behavior

– Dialysis may re-injure the kidneys as a result

Intrinsic ARF

– Tubular • Cytotoxic

– Crystals » Tumor lysis syndrome» Ethylene glycol poisoning» Megadose vitamin C» Acyclovir» Indinavir » Methotrexate

– Drugs » Aminoglycosides» Lithium » Amphotericin B» Pentamidine» Cisplatin» Ifosfamide» Radiocontrast agents

A few words about markers of renal

failure

Relationship Between GFR and Serum Creatinine in ARF

120

40

80

0

GFR(mL/min)

0 7 14 21 28

4

Days

2

0

6

Serum Creatinine(mg/dL)

Serum Creatinine

• Creatinine is more specific at assessing renal function than BUN but it corresponds only loosely to GFR [13–15].

• For example, a serum creatinine (SCrt)of 1.5 mg/dL (133 mmol/L), at steady-state, corresponds to a GFR of approximately 36 mL/min in an 80-year-old white woman, but approximately77 mL/min in a 20-year-old black man.

Creatinine and the critically ill patient

• Creatinine is formed from nonenzymatic dehydration of creatine in the liver; 98% of the creatine pool is in muscle.

• Critically ill patients may have abnormalities in liver function and markedly decreased muscle mass.

• Additional factors that influence creatinine levels include conditions of increased production (eg, trauma, fever, immobilization) or conditions of decreased production (eg, liver disease, decreased muscle mass, aging).

Creatinine and the critically ill patient

• In addition, tubular reabsorption (‘‘back-leak’’) may occur in conditions that are associated with decreased urine flow rate.

• Finally, the volume of distribution (VD) for creatinine (total body water) influences SCrt and may be increased dramatically in critically ill patients; in the short term, its concentration in plasma can be altered dramatically by rapid plasma volume expansion. The creatinine is diluted by extra volume.

Urine Output• commonly measured parameter of renal function in the ICU and is more sensitive to changes in renal hemodynamics than biochemical markers of solute clearance; however, it is far less specific except when severely reduced or absent

• severe ARF can exist despite normal urine output (ie, nonoliguric ARF) but changes in urine output often occur long before biochemical changes are apparent

• nonoliguric ARF has a lower mortality rate than oliguric ARF, thus urine output is used to differentiate ARF conditions

• Classically, oliguria is defined (approximately) as urine output of less than 5mL/kg/d or 0.5 mL/kg/h; however, no study exists to diagnose when oliguria is a true early marker of developing renal failure

Modification of Diet in Renal Disease (MDRD) Calculation for

GFR

The Cockcroft-Gault formula is calculated from the patient's age, body weight, and serum creatinine level. The MDRD uses the serum creatinine level and age alone to estimate GFR, with adjustments for sex and African American race. (>90 = normal)

Cockcroft Equation: GFR = 140 - AGE X Pt WT X 0.85 Serum Creat 70 for female

New markers for ARF

• Creatinine is not very sensitive• Cystatin C may identify ARF 1.5 days earlier than creatinine– KI 2004; 60:1115-1122

• KIM-1 Kidney Integrelin Molecule• NGAL another Integrelin, which leaks into the urine after tubular cell death.

Acute Kidney Injury Network (AKIN)

Clinical Features of Acute Renal Failure

General ManagementPre-renal

Pathophysiology of ATNOther Intrinsic Causes of ARF.

Reason for Nephrology Consultation

Reason for Nephrology Consultation

60%60%

15%15%

25%25%

Ref: Paller Sem Neph 1998, 18(5), 524.Ref: Paller Sem Neph 1998, 18(5), 524.

Approach to ARF

• Pre-Renal• Intra-Renal• Post- Renal• Pseudo-ARF

– There are other things which can raise the BUN and Creatinine!

Approach to ARF

• Pre-Renal– Most common– Due to NPO, Diuretics, ACE inhibitors, NSAIDS

– Due to renal artery disease, CHF with poor EF.

– Usually BUN / creat ratio over 20.– Usually creat < 2.5

Approach to ARF

• Intra-Renal– Most commonly pre-renal tipping over into true renal injury.

– Acute Tubular Necrosis is result (70%)

– Tubulo-Interstitial Nephritis (20%)

– Acute vasculitis/GN rare (5-10 %)

Intrinsic Renal Failure

• Prerenal ARF• Intrinsic ARF

– acute tubular necrosis– acute interstitial nephritis– acute glomerulonephritis– acute vascular syndromes– intratubular obstruction

• Postrenal ARF

Instigating Factors for ARF in a Referral

Hospital

Instigating Factors for ARF in a Referral

Hospital

30%30%

11%11%

12%12%

12%12%

30%30%

5%5%

Ref: Paller Sem Neph 1998, 18(5), 524.Ref: Paller Sem Neph 1998, 18(5), 524.

Approach to ARF

• Post- Renal– Most commonly due to obstruction at bladder outlet

• Prostate problems• Neurogenic bladder• Stone• Urethral stricture (esp after CABG)

Initial Treatment of ARF

• Fluid Resuscitation• Always place Foley Catheter• Stop offending agents

– NSAIDS, Contrast, ACE/ARB, potassium

• Watch labs• Consider diuretics/Natrecor

Acute Renal Failure

• Definitions– Azotemia - the accumulation of nitrogenous wastes

– Uremia - symptomatic renal failure– Oliguria - urine output < 400-500 mL/24 hours

– Anuria - urine output < 100 mL/24 hours

Acute Renal failure: Cause

• Acute renal failure is an abrupt renal impairment, presenting in a fall of GFR within hours or days.

• The result is a severe imbalance of fluid and electrolyte homeostasis accompanied by accumulation of nitrogenous waste.

• Occurs in response to a variety of insults– Hemodynamic– Immunological– Toxic– obstructive

Acute Renal failure

Differentiation between Pre-renal, renal and post-renal causes

Causes of acute renal failure

Prerenal Intrinsic Renal Postrenal

HypovolemiaDecreased active blood volumeDecreased cardiac outputRenovascular obstruction

Acute tubular necrosisInterstinal nephritisGlomerular disease (acute glomerulonephritis)Small vessel dieaseIntrarenal vasoconstriction (in sepsis)Tubular obstruction

Bilateral ureteric obstructionUnilateral ureteric obstructionBladder outflow obstruction

Often result of renal ischemia death of tubular cells

or direct toxic injury by endogenous chemicals such as myoglobin (from muscle rhabdomyolysis)

Integrity of tubule is destroyed

obstructions, back-leakage

Acute Renal failure

Hyperkalemia ( ECG abnormalities)

Decreased bicarbonate (acidosis)

Elevated urea

Elevated creatinine

Elevated uric acid

Hypocalcemia

Hyperphosphatemia

Complications of acute renal failure

In many cases kidney can recover from acute renal failure

The function may have to be temporarily replaced by dialysis for 2 days to 2 weeks

disturbed fluid or electrolyte homeostasis must be balanced

primary causes like necrosis, drug toxicity or obstruction must be treated

Manifestations of ARF

• Azotemia progressing to uremia• Hyperkalemia• Metabolic acidosis• Volume overload• Hyperphosphatemia• Accumulation and toxicity of medications excreted by the kidney

Pathogenesis of Prerenal Azotemia

RenalVasoconstriction

DecreasedGFR

Angiotensin II

Adrenergic nerves

Vasopressin

+

+

+

Nitric oxide

Prostaglandins-

-

VolumeDepletion

CongestiveHeart Failure Liver

Failure

SepsisSeptic Shock

Low CardiacOutput

Prerenal Acute Renal Failure

• BUN:Creatinine ratio– > 20:1

• Urine indices– Oliguria

• usually < 500 mL/24 hours; but may be non-oliguric

– Elevated urine concentration• UOsm > 700 mmol/L• specific gravity > 1.020

– Evidence of high renal sodium avidity• UNa < 20 mmol/L• FENa < 0.01

– Inactive urine sediment

AcuteTubularNecrosis

AcuteInterstitialNephritis

AcuteGN

AcuteVascular

Syndromes

IntratubularObstruction

Classification of the Etiologies of Acute Renal

Failure

PrerenalARF

PostrenalARF

IntrinsicARF

AcuteRenal

Failure

Intrinsic Acute Renal Failure

• Acute tubular necrosis (ATN)• Acute interstitial nephritis (AIN)

• Acute glomerulonephritis (AGN)• Acute vascular syndromes • Intratubular obstruction

Acute Tubular Necrosis


• Ischemic• prolonged prerenal azotemia

• hypotension• hypovolemic shock

• cardiopulmonary arrest

• cardiopulmonary bypass

• Sepsis

• Nephrotoxic– drug-induced

• radiocontrast agents

• aminoglycosides• amphotericin B• cisplatinum• acetaminophen

– pigment nephropathy

• hemoglobin• myoglobin

Pathophysiology of ATN:Tubular Epithelial Cell

Injury and Repair

Loss of Loss of polaritypolarity

Normal Normal EpitheliumEpithelium

Migration , Dedifferentiation of Migration , Dedifferentiation of Viable CellsViable Cells

DifferentiatioDifferentiation & n & ReestablishmenReestablishment of polarityt of polarity

Sloughing of viable and dead Sloughing of viable and dead cells with luminal obstructioncells with luminal obstruction

Ischemia/ Ischemia/ ReperfusioReperfusio

nn ApoptosiApoptosiss

Necrosis

Cell deathCell death

Adhesion moleculesNa+/K+-ATPase

ProliferationProliferation

Pathophysiology of ATN

Ischemia

Endothelial Injury

Capillary Obstruction&

Continued Ischemia

Inflammation

Tubular Injury

Disruption of Cytoskeleton

Loss of Cell Polarity

Desquamation of Cells

Tubular Obstruction&

Backleak

Apoptosis&

Necrosis

Activation of VasoconstrictorsImpaired Vasodilation

Increased Leukocyte Adhesion

Pathophysiology of Acute Tubular Necrosis

• Mechanisms of decreased renal function– Vasoconstriction– Tubular obstruction by sloughed debris

– Backleak of glomerular filtrate across denuded tubular basement membrane

Acute Tubular NecrosisUrinary Findings


• Urine indices– Urine volume

• may be oliguric or non-oliguric– Isosthenuric urine concentration

• UOsm 300 mmol/L• specific gravity 1.010

– Evidence of renal sodium wasting• UNa > 40 mmol/L• FENa > 0.02

– Urine sediment• tubular epithelial cells• granular casts

• BUN: Creatinine ratio = 10:1• Evidence of toxin exposure

Phases of Ischemic ATN

Prerenal

Initiation

Extension

Maintenance Recove

ry

GF

R

Time: 2 days to 2 weeks typical

Prognosis ofAcute Tubular Necrosis

• Mortality dependent upon comorbid conditions– overall mortality ~ 50%

• Recovery of renal function seen in ~ 90% of patients who survive - although not necessarily back to prior baseline renal function

Time for a break

Acute Renal Failure

Documents

Transcript of Acute Renal Failure