25 chen acute renal failure

Update on Acute Renal Update on Acute Renal Failure 2.0Failure 2.0

Kenneth Chen, M.D.

Cases of ARF Among Medicare Inpatients

10

15

20

25

30

35

40

Cas

es p

er 1

000

dis

char

ges

Year

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

JASN 17:1135-1142, 2006

Incidence of Non-Dialysis ARF Incidence of Non-Dialysis ARF

Kidney Int 2007

Incidence of Dialysis-Requiring ARFIncidence of Dialysis-Requiring ARF

KI 2007

KI 74:101, 2008

0

5

10

15

20

25

30

35

40

45

No Dialysis

Dialysis

YearJASN 17:1143, 2006

1988 1990 1992 1994 1996 1998 2000 2002

Mort

alit

y (

%)

Inpatient Mortality - ARF

Inpatient Mortality From ARFInpatient Mortality From ARF

0

10

20

30

40

50

60

1988-1992 1993-1997 1998-2002

Mor

talit

y (%

)

CI 0

CI 1

CI 3

CI 5

JASN 17:1143, 2006

Inpatient Mortality From ARF-DInpatient Mortality From ARF-D

05

101520253035404550

1988-1992 1993-1997 1998-2002

Mor

talit

y (%

)

CI 0

CI 1

CI 3

CI 5

JASN 17:1143, 2006

Increase in Total Cost of Hospitalization

Increase in Serum Creatinine from Baseline

JASN 2005;16:3365

RIFLE and AKIN staging criteria for AKIRIFLE and AKIN staging criteria for AKI____________________________________________________________________________________________________________________________

RIFLE AKIN Serum Cr Urine OutputRIFLE AKIN Serum Cr Urine Output

Stage Stage Criteria CriteriaStage Stage Criteria Criteria

____________________________________________________________________________________________________________________________

Risk 1 Increase in Scr of 1.5-2x < 0.5 ml/kg/hrRisk 1 Increase in Scr of 1.5-2x < 0.5 ml/kg/hr

baseline or increase >0.3 for 6 hrsbaseline or increase >0.3 for 6 hrs

Injury 2 Increase in Scr of 2-3x < 0.5 ml/kg/hrInjury 2 Increase in Scr of 2-3x < 0.5 ml/kg/hr

baseline for 12 hrsbaseline for 12 hrs

Failure 3 Increase in Scr of more < 0.3 ml/kg/hrFailure 3 Increase in Scr of more < 0.3 ml/kg/hr

than 3x baseline or Scr >4 for 24 hrthan 3x baseline or Scr >4 for 24 hr

with an acute rise of > 0.5 orwith an acute rise of > 0.5 or

anuria for 12 anuria for 12 hrhr

LossLoss Persistent renal failure > 4 wk Persistent renal failure > 4 wk

ESRD Persistent renal failure > 3 moESRD Persistent renal failure > 3 mo

Causes of Hospital-Acquired AKICauses of Hospital-Acquired AKI

ATN (45%)ATN (45%) Prerenal (21%)Prerenal (21%) Acute on Chronic (13%)Acute on Chronic (13%) Postrenal (10%)Postrenal (10%) Renal Vascular (3%)Renal Vascular (3%) Glomerulonephritis (3%)Glomerulonephritis (3%) AIN (2%)AIN (2%) Atheroemboli (1%)Atheroemboli (1%) Kidney Int 50:811, 1996Kidney Int 50:811, 1996

Causes of Community-Acquired Causes of Community-Acquired AKIAKI

1% of hospital admissions:1% of hospital admissions:

70% prerenal azotemia70% prerenal azotemia

17% obstruction17% obstruction

11% intrinsic (mostly drug- 11% intrinsic (mostly drug-

induced)induced)

Kaufman AJKD 1991Kaufman AJKD 1991

Prerenal ARFPrerenal ARF Volume depletionVolume depletion Decreased Effective Circulating Decreased Effective Circulating

Volume – cirrhosis, CHF, nephrotic Volume – cirrhosis, CHF, nephrotic syndrome, sepsissyndrome, sepsis

Altered Intrarenal Hemodynamics – Altered Intrarenal Hemodynamics – NSAIDS, Hypercalcemia, hepatorenal NSAIDS, Hypercalcemia, hepatorenal syndrome, ACEI, ARB, calcineurin syndrome, ACEI, ARB, calcineurin inhibitorsinhibitors

Urinary IndicesUrinary Indices

Prerenal – UPrerenal – UNaNa < 20 mEq/L < 20 mEq/L

FEFENaNa< 1% < 1%

FEFEureaurea<35% (PPV 98%)<35% (PPV 98%)

ATN – UATN – UNaNa > 40 mEq/L > 40 mEq/L

FEFENaNa>2%>2%

Kidney Int 2002;62:2223 Kidney Int 2002;62:2223

Intrinsic AKIIntrinsic AKI ATN – ischemic (bypass, arrest, sepsis, ATN – ischemic (bypass, arrest, sepsis,

shock) or toxic (drug-induced or pigment shock) or toxic (drug-induced or pigment nephropathy)nephropathy)

AIN – drugs, herbs, infections, malignancyAIN – drugs, herbs, infections, malignancy Acute GN – post-infectious GN, vasculitis, Acute GN – post-infectious GN, vasculitis,

endocarditis, HUS/TTPendocarditis, HUS/TTP Acute vascular syndromes – Acute vascular syndromes –

atheroembolic dz, renal artery atheroembolic dz, renal artery thromboembolism, renal artery dissection, thromboembolism, renal artery dissection, renal vein thrombosisrenal vein thrombosis

Diagnosis of ATNDiagnosis of ATN

Granular castsGranular casts Very little or no proteinuriaVery little or no proteinuria High FENa > 2% (exception contrast)High FENa > 2% (exception contrast) Consistent clinical scenario i.e. Consistent clinical scenario i.e.

sepsis, contrast, hypotensionsepsis, contrast, hypotension

““Muddy” (Pigmented) Granular Muddy” (Pigmented) Granular CastsCasts

RBC CastRBC Cast

Dysmorphic RBCsDysmorphic RBCs

Acute Phosphate NephropathyAcute Phosphate Nephropathy

Complication of phosphate Complication of phosphate containing bowel cleansing regimens containing bowel cleansing regimens e.g. Fleet’s, Visicol, tablet formse.g. Fleet’s, Visicol, tablet forms

Risk factors – elderly (mean age 64), Risk factors – elderly (mean age 64), hx of HTN, ACEI or ARBhx of HTN, ACEI or ARB

Can present 1 mo after colonoscopyCan present 1 mo after colonoscopy Normocalcemia and bland urinary Normocalcemia and bland urinary

sedimentsediment JASN 16:3389, 2005JASN 16:3389, 2005

NephrotoxinsNephrotoxins

Afferent arteriolar constriction –Afferent arteriolar constriction –

NSAIDsNSAIDs

ContrastContrast

Amphotericin BAmphotericin B

VancomycinVancomycin

NorepinephrineNorepinephrine

Efferent arteriolar dilation – Efferent arteriolar dilation –

ACEIACEI

ARBARB

NephrotoxinsNephrotoxinsCrystalluria – sulfonamidesCrystalluria – sulfonamides

methotrexatemethotrexate acyclovir (risk 19%)acyclovir (risk 19%)

triamterene triamterene ethylene glycolethylene glycol

indinavirindinavirPigmenturia – myoglobinuriaPigmenturia – myoglobinuria hemoglobinuriahemoglobinuriaGlomerulonephritis – hydralazineGlomerulonephritis – hydralazineHUS/TTP – gemcitabine, quinine, clopidogrel, HUS/TTP – gemcitabine, quinine, clopidogrel,

cyclosporine, tacrolimuscyclosporine, tacrolimus

NephrotoxinsNephrotoxins

Tubular toxicity – aminoglycosidesTubular toxicity – aminoglycosides

cisplatincisplatin

vancomycinvancomycin

pentamidinepentamidine

contrastcontrast

amphotericin Bamphotericin B

heavy metalsheavy metals

tenofovir (Viread), didanosine (Videx), tenofovir (Viread), didanosine (Videx), lamivudine (Epivir), stavudine (Zerit)lamivudine (Epivir), stavudine (Zerit)

AINAIN

Drug related in 92% of casesDrug related in 92% of cases Oliguria (51%), arthralgia (45%), Oliguria (51%), arthralgia (45%),

peripheral eosinophilia (36%), fever peripheral eosinophilia (36%), fever (30%), rash (21%)(30%), rash (21%)

Urine eosinophils (40%) – PPV 38%Urine eosinophils (40%) – PPV 38% Proteinuria - 0.7 g/dayProteinuria - 0.7 g/day No proven benefit from steroids No proven benefit from steroids

Nephrol Dial Transplant 2004;19:2778Nephrol Dial Transplant 2004;19:2778

AINAIN

Causes of Interstitial NephritisCauses of Interstitial Nephritis

NSAIDs and 5-aminosalicylates NSAIDs and 5-aminosalicylates

Aristolochic Acid (Chinese herb nephropathy)Aristolochic Acid (Chinese herb nephropathy)

Lymphoma, sarcoidosis, Sjogren’sLymphoma, sarcoidosis, Sjogren’s

Antibiotics – Nafcillin, rifampin, PCN, Antibiotics – Nafcillin, rifampin, PCN, cephalosporins, bactrim, ciprofloxacin, cephalosporins, bactrim, ciprofloxacin, vancomycin, indinavirvancomycin, indinavir

Dilantin, phenobarbital, carbamazepineDilantin, phenobarbital, carbamazepine

Allopurinol, H2-blockers, PPIsAllopurinol, H2-blockers, PPIs

Sulfonamides – HCTZ, bactrim, LasixSulfonamides – HCTZ, bactrim, Lasix

CINCIN 33rdrd leading cause of inpatient ARF – leading cause of inpatient ARF –

12%12% Overall incidence 1.6-2.3% but in Overall incidence 1.6-2.3% but in

patients with CKD 15-50%patients with CKD 15-50% 13-50% requiring HD after contrast 13-50% requiring HD after contrast

remain on dialysis permanentlyremain on dialysis permanently Risk factors include CKD, DM, Risk factors include CKD, DM,

diuretics, hypovolemia, CHF, diuretics, hypovolemia, CHF, proteinuriaproteinuria

JAMA 2006;295(23):2765 and NEJM 2006;354:379JAMA 2006;295(23):2765 and NEJM 2006;354:379

CINCIN

Omnipaque (iohexol) – low-osmolar Omnipaque (iohexol) – low-osmolar (400-850 mOsm/kg), nonionic(400-850 mOsm/kg), nonionic

Visipaque (iodixanol) – iso-osmolar Visipaque (iodixanol) – iso-osmolar (290 mOsm/kg), nonionic(290 mOsm/kg), nonionic

% Incidence of CIN% Incidence of CIN

NEJM 2003;348(6):491

J Am Coll Cardiol 2006;48(4):692

CINCIN

Arch Intern Med 2002;162:329

CINCIN

NEJM 2000;343:180

CINCIN

Eur Heart J 2004;25:206

CINCIN

NEJM 2006;354:2773

CINCIN

JAMA 2004;291(19):2328

CINCIN

Clin J Am Soc Nephrol 2008;3:10

CINCIN

A meta-analysis of 41 controlled trials A meta-analysis of 41 controlled trials examining various prophylactic agents examining various prophylactic agents showed only NAC reduced the risk for showed only NAC reduced the risk for CIN (RR 0.62) over saline aloneCIN (RR 0.62) over saline alone

Furosemide increased the risk of CIN Furosemide increased the risk of CIN (RR 3.27)(RR 3.27)

Ann of Int Med 2008;148:284Ann of Int Med 2008;148:284

CIN - SummaryCIN - Summary Check a Cr if hx of CKD, DM, proteinuria, Check a Cr if hx of CKD, DM, proteinuria,

renal surgery, CHF, gout, or HTNrenal surgery, CHF, gout, or HTN Hold NSAIDs and diuretics for 24 hrs Hold NSAIDs and diuretics for 24 hrs

before and after contrast, and metformin before and after contrast, and metformin the day of the procedure.the day of the procedure.

NAC 1200 mg PO bid 24 hrs before and NAC 1200 mg PO bid 24 hrs before and after contrast after contrast

NS 1 ml/kg/hr 6-12 hrs before and after NS 1 ml/kg/hr 6-12 hrs before and after contrast contrast

Approach to DiagnosisApproach to Diagnosis

History - NSAIDs, herbals, medications, History - NSAIDs, herbals, medications, contrast, UTI symptoms, prostatism?contrast, UTI symptoms, prostatism?

Physical – suprapubic Physical – suprapubic fullness/tendernessfullness/tenderness

Bladder catheterization and/or U/SBladder catheterization and/or U/S

U/A and urinary indicesU/A and urinary indices

Therapeutic trial of IVFsTherapeutic trial of IVFs

CrCl = (140-age) x IBW/(Cr x 72) x 0.85 if female

Cockcroft-Gault Equation

Treatment of ARFTreatment of ARF IVF hydrationIVF hydration Early removal of Foley cathetersEarly removal of Foley catheters General lack of benefit – mannitol, loop General lack of benefit – mannitol, loop

diuretics, low dose dopaminediuretics, low dose dopamine Renal dose medications – especially Renal dose medications – especially

antibioticsantibiotics Adjust TPN/lower K and PO4 intakeAdjust TPN/lower K and PO4 intake Avoid PICC lines – 23% initial thrombosis Avoid PICC lines – 23% initial thrombosis

risk and 38% thrombosis risk overall risk and 38% thrombosis risk overall (JVIR (JVIR 2000;11:1309)2000;11:1309)

Treatment of ARFTreatment of ARF Stop metformin if Cr > 1.5Stop metformin if Cr > 1.5 Switch from tolazamide or glyburide to Switch from tolazamide or glyburide to

glipizideglipizide Avoid gemfibrozil and statinsAvoid gemfibrozil and statins Avoid Demerol, aminoglycosides, NSAIDs, Avoid Demerol, aminoglycosides, NSAIDs,

Fleet’s enemas, Al, MgFleet’s enemas, Al, Mg Caution with morphine, insulin, fosamax, Caution with morphine, insulin, fosamax,

lmwhlmwh Avoid nitrofurantoin or probenecidAvoid nitrofurantoin or probenecid Use ½ NS for post-obstructive diuresisUse ½ NS for post-obstructive diuresis

Treatment of ARFTreatment of ARF

Indications for dialysis:Indications for dialysis:

Refractory metabolic acidosisRefractory metabolic acidosis

Refractory hyperkalemiaRefractory hyperkalemia

Pulmonary edema/volume overloadPulmonary edema/volume overload

Uremic pericarditisUremic pericarditis

Uremic symptomsUremic symptoms

Toxic ingestionsToxic ingestions

Nephrogenic Systemic FibrosisNephrogenic Systemic Fibrosis

Hardening and thickening of skin Hardening and thickening of skin overlying the trunk and extremitiesoverlying the trunk and extremities

Expansion and fibrosis of the dermis Expansion and fibrosis of the dermis in association with CD34-positive in association with CD34-positive fibrocytesfibrocytes

95% of cases associated with 95% of cases associated with gadoliniumgadolinium

Probably 5% risk in advanced RFProbably 5% risk in advanced RF

Nephrogenic Systemic FibrosisNephrogenic Systemic Fibrosis

Nephrogenic Systemic FibrosisNephrogenic Systemic Fibrosis

Nephrogenic Systemic FibrosisNephrogenic Systemic Fibrosis

Nephrogenic Systemic FibrosisNephrogenic Systemic Fibrosis

Gd should be avoided when GFR<30Gd should be avoided when GFR<30 Dialysis should be initiated as soon Dialysis should be initiated as soon

as possible after exposure if pt is on as possible after exposure if pt is on dialysisdialysis

No proven treatment No proven treatment

Ancient Chinese Medical TextAncient Chinese Medical Text

The inferior doctor treats actual The inferior doctor treats actual illness.illness.

The mediocre doctor attends to The mediocre doctor attends to impending illness.impending illness.

The superior doctor prevents illness The superior doctor prevents illness (Kaiser Permanente!)(Kaiser Permanente!)

2600 BC - Huang Dee Nai-Chang 2600 BC - Huang Dee Nai-Chang

D’oh!

Evidence-Based MedicineEvidence-Based Medicine Eminence-Based MedicineEminence-Based Medicine Eloquence-Based MedicineEloquence-Based Medicine Vehemence-Based MedicineVehemence-Based Medicine Kaiser-Based MedicineKaiser-Based Medicine

CINCIN

NDT 2006;21(8):2120

CINCIN

Ann of Pharmacotherapy 2007;41:46

Causes of ProteinuriaCauses of Proteinuria

Selected Causes of Proteinuria by TypeSelected Causes of Proteinuria by Type

Glomerular Glomerular Primary glomerulonephropathy Minimal change disease Primary glomerulonephropathy Minimal change disease Idiopathic membranous glomerulonephritis Focal segmental Idiopathic membranous glomerulonephritis Focal segmental glomerulonephritis Membranoproliferative glomerulonephritis IgA glomerulonephritis Membranoproliferative glomerulonephritis IgA nephropathy Secondary glomerulonephropathy Diabetes mellitus Collagen nephropathy Secondary glomerulonephropathy Diabetes mellitus Collagen vascular disorders (e.g., lupus nephritis) Amyloidosis Preeclampsia vascular disorders (e.g., lupus nephritis) Amyloidosis Preeclampsia Infection (e.g., HIV, hepatitis B and C, poststreptococcal illness, syphilis, Infection (e.g., HIV, hepatitis B and C, poststreptococcal illness, syphilis, malaria and endocarditis) Gastrointestinal and lung cancers Lymphoma, malaria and endocarditis) Gastrointestinal and lung cancers Lymphoma, chronic renal transplant rejection Glomerulonephropathy associated with chronic renal transplant rejection Glomerulonephropathy associated with the following drugs: Heroin NSAIDs Gold components Penicillamine Lithium the following drugs: Heroin NSAIDs Gold components Penicillamine Lithium Heavy metals Heavy metals

TubularTubular Hypertensive nephrosclerosis Tubulointerstitial disease due to: Hypertensive nephrosclerosis Tubulointerstitial disease due to: Uric acid nephropathy Acute hypersensitivity interstitial nephritis Fanconi Uric acid nephropathy Acute hypersensitivity interstitial nephritis Fanconi syndrome Heavy metals Sickle cell disease NSAIDs, antibiotics syndrome Heavy metals Sickle cell disease NSAIDs, antibiotics

Overflow Overflow Hemoglobinuria Myoglobinuria Multiple myeloma Amyloidosis Hemoglobinuria Myoglobinuria Multiple myeloma Amyloidosis

In-Hospital Mortality Rate 1992-In-Hospital Mortality Rate 1992-20012001

33% - ARF requiring dialysis33% - ARF requiring dialysis

27.5% - ARF not requiring dialysis27.5% - ARF not requiring dialysis

4.6% - no ARF4.6% - no ARF

JASN 17:1135-1142, 2006JASN 17:1135-1142, 2006

Survival in ESRDSurvival in ESRD

Life expectancy for a 40 year-old male Life expectancy for a 40 year-old male is 37.3 years, but just 7.4 yrs on is 37.3 years, but just 7.4 yrs on dialysisdialysis

Life expectancy for a 60 year-old male Life expectancy for a 60 year-old male is 20.2 years, but just 4 yrs on dialysisis 20.2 years, but just 4 yrs on dialysis

Life expectancy for a 70 year-old male Life expectancy for a 70 year-old male is 13.2 years, but just 2.8 yrs on is 13.2 years, but just 2.8 yrs on dialysisdialysis

USRDSUSRDS

Causes of Hospital-Acquired ARFCauses of Hospital-Acquired ARF

Postoperative statePostoperative state Advanced cardiovascular diseaseAdvanced cardiovascular disease Neoplastic diseaseNeoplastic disease HIV infectionHIV infection Multiple organ system failureMultiple organ system failure Systemic infectionSystemic infection Solid organ transplantationSolid organ transplantation

Increase in Serum Creatinine from Baseline

JASN 2005;16:3365

CaseCase

65 y.o. female admitted with fevers, hearing 65 y.o. female admitted with fevers, hearing loss, ear pain, neck pain, vomiting, and loss, ear pain, neck pain, vomiting, and myalgias.myalgias.

Meds – lisinopril 15 mg dailyMeds – lisinopril 15 mg daily

HCTZ 25 mg dailyHCTZ 25 mg daily

Labs – Na 139 K 3.6 Cl 101 HCO3 25 BUN 13 Labs – Na 139 K 3.6 Cl 101 HCO3 25 BUN 13 Cr 0.7 Gluc 149Cr 0.7 Gluc 149

U/A (catheter) 1.02/6/50 mg% ketones/large U/A (catheter) 1.02/6/50 mg% ketones/large bl/30 mg% prot/sm LE/5-10 sq cells/0-2 bl/30 mg% prot/sm LE/5-10 sq cells/0-2 WBC/11-25 RBCWBC/11-25 RBC

CaseCase11stst Day – ceftriaxone (2g q12, vanco (1 g), IV Day – ceftriaxone (2g q12, vanco (1 g), IV

acyclovir 10 mg/kg q8hr)acyclovir 10 mg/kg q8hr)

22ndnd day – vanco and acyclovir d/c’d day – vanco and acyclovir d/c’d

Scr 0.6Scr 0.6

33rdrd day – aspirin 162 mg daily and lisinopril day – aspirin 162 mg daily and lisinopril startedstarted

Scr 1.97 U/A 100 mg%prot/5-10 sq cells/3-Scr 1.97 U/A 100 mg%prot/5-10 sq cells/3-5 WBC/10-25 RBC5 WBC/10-25 RBC

44thth day – Scr 2.2 U/A tr prot/sm LE/3-5 day – Scr 2.2 U/A tr prot/sm LE/3-5 WBC/0-2 RBCWBC/0-2 RBC

55thth day – Scr 1.4 day – Scr 1.4

CaseCase

What was the cause of her ARF?What was the cause of her ARF?

a)a) VancomycinVancomycin

b)b) AcyclovirAcyclovir

c)c) CeftriaxoneCeftriaxone

d)d) Volume contractionVolume contraction

e)e) SepsisSepsis

90 Day Mortality Rate in 200190 Day Mortality Rate in 2001

44.8% - ARF requiring dialysis44.8% - ARF requiring dialysis 40.3% - ARF not requiring dialysis40.3% - ARF not requiring dialysis 12.1% - no ARF12.1% - no ARF

JASN 17:1135-1142, 2006JASN 17:1135-1142, 2006