02 radhakrishnan acute renal failure update

Acute Renal FailureAn Update

Jai Radhakrishnan, MD, MS, FASN, FACCAssociate Professor of Clinical Medicine

Columbia University

Objectives

Epidemiology of ARF

Diagnostic workup

Specific syndromes of ARF

Treatment and Prevention

ARF-Definitions Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group Crit Care. 2004 Aug;8(4):R204

Changes in mortality in patients with acute renal failure over 47 years

Ympa YP Am J Med. 2005 Aug;118(8):827-32.

Etiology of ARF

Pre-renal (hemodynamic)

Intra-Renal (parenchymal)

Post-renal (obstructive)

ARF: Pre-renal

Volume DepletionCardiacRedistributionHepatorenalsyndrome

NSAIDSACE-inhibitors

Prostaglandins Angiotensin-II

Hepatorenal Syndrome: Diagnostic Criteria

Hepatology. 1996 Jan;23(1):164-76

MAJOR CRITERIA: Chronic/Acute liver disease with advanced hepatic failure and portal hypertensionLow GFR (Creatinine>1.5mg/dL or CrCl<40ml/min)Absence of shock, bacterial infection, nephrotoxin, GI /renal fluid lossesNo sustained renal improvement after withdrawing diuretics and volume expansion (1.5 L NS)Proteinuria<500mg/d and renal usg without obstruction or parenchymal abnormality

MINOR CRITERIAUrine Volume <500ml/dayUrine Na <10meq/LUrine RBC<50/HPFSerum Na <130meq/L

100100

9090

8080

7070

6060

5050

4040

3030

2020

1010

00--1414 --1313 --1212 --1111 --1010 --99 --88 --77 --66 --55

Agonist (Log M)Agonist (Log M)

Edwards AJP 1989Edwards AJP 1989

AVPAVPNENE

100100

9090

8080

7070

6060

5050

4040

3030

2020

1010

00--1414 --1313 --1212 --1111 --1010 --99 --88 --77 --66 --55

Agonist (Log M)Agonist (Log M)

AVPAVPNENE

% R

educ

tion

in L

umen

Dia

met

er%

Red

uctio

n in

Lum

en D

iam

eter

Efferent and Afferent Arterioles of Rabbit

Efferent Afferent

Terlipressin +/- Albumin In HRS

Hepatology 36 (2002), pp. 941–948

Hepatorenal Syndrome Type I: Vasopressin in One Patient

120120

100100

8080

6060

4040

2020

00

120120

100100

8080

6060

4040

2020

00--66 --44 --22 00 22 44 66 88

SBP SBP (mm Hg)(mm Hg)

Time (hrs)Time (hrs)

AVPAVP

SPASPA

SBP SBP (mm Hg)(mm Hg)

UOUO(cc/h)(cc/h)

UOUO(cc/h)(cc/h)

Diclofenac Residues as the Cause of Vulture population Decline in Pakistan

Nature. 2004 Feb 12;427(6975):

ARF: Post-renal

Consider obstruction in every patient with ARF.Sites of obstruction leading to ARF:

Bladder neck obstructionBilateral ureters

Urine volume variable.Renal USG or Bladder catheterization.

ARF: Intra-Renal

VASCULARVascular occlusionAtheroembolicdiseaseThrombotic microangiopathy

INTERSTITIALInterstitial nephritis

GLOMERULARAcute/Rapidly progressive glomerulonephritis

TUBULARCrystal ATN

Atheroembolic disease

ARF precipitated by angiographyOften eosinophilia and low complementMulti-organ dysfunction, livedo reticularis, blue toesGenerally irreversible

Acute Interstitial Nephritis

Triad of fever, skin rash and eosinophiliaEosinophiluriaDrugs: penicillin, cephalosporins, diuretics, NSAIDS, dilantinUsually completely reversible upon withdrawing drug?Glucocorticoids

Rapidly Progressive Glomerulonephritis

ETIOLOGYImmune complex GN: -post infectious,SLE, IgAN, SBE, cryoglobulinemiaAnti GBM antibody diseaseVasculitis: -Wegener’s, microscopic PAN, idiopathic crescentic GN

DIAGNOSTIC CLUESSystemic findingsSignificant proteinuria, RBC, RBC casts

Crystal-induced ARF

Uric acid (tumor-lysis)Oxalate (ethylene glycol)MethotrexateAcyclovirSulfonamidesIndinavirPhospho Soda

Uric Acid

Oxalate

Indinavir- Urine Crystals

Gagnon RF.. Am J Kidney Dis 2000 Sep;36(3):507-515

Osmotic Nephrosis

SucroseMannitolIntravenous immunoglobulinRadiocontrast agents

DextranHydroxyethyl starch

Ebcioglu Z.. Kidney International (2006) 70, 1873–1876.

J Am Soc Nephrol. 2005 Nov;16(11):3389-96.

Etiology of ATN

IschemicAll pre-renal causes

Exogenous ToxinsAntibioticsContrastChemotherapyOrg. solvents, Heavy metals

Endogenous Toxins

HemoglobinMyoglobinLight chains

Radiocontrast NephropathyClinical Course:

Onset of oliguria within 24 hoursPeak creatinine in 4-5 days followed by recovery in the majorityDifferential diagnosis: atheroembolic disease

Risk factors: AgeChronic kidney disease esp. diabetesPre-renal azotemia (e.g. cirrhosis, CHF)Volume of contrast

Contrast Nephropathy RiskS Creatinine> 0.5 mg/dl or > 25%at 48-72 h

Mehran R.. J Am Coll Cardiol. 2004 Oct 6;44(7):1393-9.

Heme Pigment Induced ATN

Rhabdomyolysis: traumatic or non-traumaticIntravascular hemolysisMechanism uncertain: Vasoconstriction, precipitation/obstruction, toxicity of other breakdown productsConcomitant volume depletion

Aminoglycoside NephrotoxicityNon-oliguric renal failureOnset several days after treatmentRecovery is usually complete within 3 weeks

Mingeot-Leclercq MP… Antimicrob Agents Chemother. 1999 May;43(5):1003-12.

Top 5 Causes of ARF

Am J Kidney Dis. 2002 May;39(5):930-6

Urinary Indices in Oliguric ARF

*UNa / PNa ÷ UCr / PCr

Urinary Index Pre-renal ATN

Osmolality (mOsom/kg)

>500 <400

Sodium (meq/L) <20 >40

Fractional ex of Na <1 % >2%

Urine Microscopy

Red Cell Cast WBC Cast

Muddy (granular) Cast Broad Cast

Workup of Renal Failure

Post-Renal

Glomerular Vascular Interstitial Tubular

Renal Pre-Renal

Acute or Chronic

RENAL FAILURE

History, Physical, Urine analysis, USG

Treatment of ATN-2005

SUPPORTIVE CARE• Acid-base/electrolyte balance• Fluid balance• Nutrition• Review of drugs• Dialysis:

• PD, HD, Continuous modalities

Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury.

N Engl J Med. 2008 May 20. [Epub ahead of print]

35 ml/kg/h

20 ml/kg/h

Course and Outcome of ATN

Am J Kidney Dis. 2002 May;39(5):930-6

Bruce A. Molitoris & Robert Bacallao

Pathogenesis of ATN

Tubuloglomerular feedback

EndothelinAdenosine

Nitric OxideProstacyclin

Source of ROS:XanthineDehydrogenaseNADH Oxidase

Pathogenesis of ATN: Reactive Oxygen Species

QUESTION: What preventive strategies have been consistently shown to be effective against ATN?

Maintaining euvolemia ?N-acetyl cysteine ?Dopamine ?Iso-osmolar contrast ?

Preventive StrategiesPOSITIVE:

HydrationEQUIVOCAL:

BicarbonateN-Acetyl CysteineTheophyllineIsoosmolar ContrastCRRT/Dialysis

NEGATIVE:Atrial natriuretic peptide Anti-endothelinantagonistFenoldopam

The Data

Effect on Mortality

Effect on need for Renal Replacement Therapy

Friedrich JO; Adhikari N; Herridge MS; Beyene J. Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death.Ann Intern Med 2005 Apr 5;142(7):510-24.

High-dose Furosemide for Established ARF

338 pts with ARF on dialysisFurosemide (25mg/kg IV or 35mg/kg PO, or matched placebo) daily.No difference in :

SurvivalRenal recovery

Shorter time to 2L/day diuresis

Am J Kidney Dis. 2004 Sep;44(3):402-9

Course and Outcome of ATN

Am J Kidney Dis. 2002 May;39(5):930-6

ARF Outcomes after Discharge: Survival979 pts who received CRRT69% in-hospital mortalityPost discharge survival:

6M: 89%5 Y: 50%

Morgera, S. American Journal of Kidney Disease 2002; 40(2):275-279

Morgera, S. American Journal of Kidney Disease 2002; 40(2):275-279

Korkeila, M. Nephrology, Dialysis, and Transplantation 2000

77% assessed health as “Good to excellent”69% resumed working57% self-sustainingMost Common Complaints:

Loss of energyDifficulty with heavy houseworkLimited physical mobility

ARF: Outcomes after DischargeQuality of Life

Future Developments

Biomarkers:Cell-based therapy

Current Status of Biomarkers

Neutrophil Gelatinase-associated Lipocalcin(NGAL)Kidney Injury Molecule-1Interleukin 18

Nickolas T.. Curr Opin Nephrol Hypertens. 2008 Mar;17(2):127-132

1514131211109876543210

25

50

75

100

125

150

175

200

225

2 4 6 8 12 24 36 48 60 72 84 96 108 120

Post CPB Time (hours)

Urin

e N

GAL

(ng/

ml)

No ARF(n=51)

ARF(n=20)

Serum Creat Rise

Urine NGAL is upregulated 15-fold within 2 hours after CPB in patients who later develop ARF

Lancet. 2005Apr;365(9466):1231-8.

2100

100

200

300

400

500

600

ARF(n=20)

No ARF(n=51)

Urin

e N

GAL

(ng/

ml)

2 hr

pos

t CPB

Urinary NGAL at 2 Hours Post CPB

50

The 2-hour urine NGAL was 50 ng/ml or higher in all patients who subsequently developed ARF

Lancet. 2005Apr;365(9466):1231-8.

Sensitivity: 100%Specificity: 98%PPV: 95%NPV: 100%

Ann Intern Med. 2008 Jun 3;148(11):810-9.

ConclusionsARF is common in hospitalized patients & has a high mortalityA significant number of patients recoverThe best (and least expensive) preventive strategy is to maintain euvolumia