Acute Renal Failure

Raymond C. Harris, M.D.

Division of Nephrology

Acute Renal Failure

• Common in the ICU setting

• May affect from 1% to 25% of patients depending on the population and the criteria used to define ARF

• 5-7% of all hospitalized patients

• High morbidity and mortality: in-hospital, 30% in nephrotoxic-drug induced ARF, 90% when respiratory, hepatic, or other organ failure present

Mortality in Acute Renal Failure

38

60

82 8490

0

20

40

60

80

100

0 1 2 3 4

Number of Organ Systems Failed *

%

* Nonrespiratory organ systems* Nonrespiratory organ systems

Chertow et al, Arch Intern Med, 1996Chertow et al, Arch Intern Med, 1996

The Effect of Acute Renal Failure on Mortality

• A cohort analysis study: 183 patients who developed contrast-induced ARF (A), 174 patients without ARF (B)

Death during hospitalizationGroup A 37%Group B 7% p<0.001

*ARF increases the risk of developing severe nonrenal complications that lead to death

Levy EM, et al. JAMA, 1996

Differential Diagnosis of Acute Renal Failure

Acute Renal FailureAcute Renal FailureAcute Renal FailureAcute Renal Failure

PrerenalPrerenalPrerenalPrerenal Intrinsic Intrinsic RenalRenal

Intrinsic Intrinsic RenalRenal

PostrenalPostrenalPostrenalPostrenal

VascularVascularVascularVascular GlomerularGlomerularGlomerularGlomerular InterstitialInterstitialInterstitialInterstitial TubularTubularTubularTubular

Prerenal ARF

• Decreased intake

• External losses (skin, GI, blood, renal)

• Internal losses (pancreatitis, ascites, edema)

• Compromised heart function (MI, tamponade, CHF)

• Increased vascular pooling (HRS, sepsis)

Intrinsic Renal ARF

• Prolonged prerenal state

• Hypotension (surgery, bleeding)

• Exposure to toxins (drugs, etc)

• Drug sensitivity

• Multisystem disease

Postrenal ARF

• H/o urinary symptoms

• H/o stones

• Sudden anuria

• H/o of pelvic tumor, disease

• H/o pelvic radiation

• H/o pelvic surgery

Physical Examination in Differential Diagnosis

• Orthostatic hypotension, heart rate

• Skin findings

• Edema, ascites

• Pelvic findings

• Examination of optic fundi

• Abdominal bruits

Urinary Electrolytes

Fractional Excretion of Sodium (FENa):

FENa=quantity of Na+ excreted

= UNa x V

= UNa x Pcr

quantity of Na+ filtered x100

x100

x100

PNa x (Ucr x V/Pcr)

PNa x Ucr

FENa< 1%= prerenal (usually)

Urine Sediment

• RBC casts GN, vasculitis

• RTE cell casts ATN

• Muddy brown casts ATN

• WBCs, Eos AIN

• Oxalate Ethylene Glycol

• Bland Prerenal, Postrenal

Prevention/Treatment of ARF

• Prevention studies exceptionally challenging

• Few viable examples in ARF, since can rarely be anticipated

• Low prevalence + Modest efficacy = Huge sample size to show effect

Prevention/Treatment of ARF

• Intravenous hydration• Renal-dose dopamine• Fenoldopam• Acetylcysteine• Atrial Natriuretic Peptide• Endothelin receptor antagonists• Growth Factors

Effects of Saline, Mannitol, and Furosemide in Renal Function

• 78 pts with CRI undergoing cardiac cath• 28 pts: 0.45% saline alone for 12 hours before

and 12 hours after angiography• 25 pts: Saline and 25 g mannitol (60 minutes

before angiography)• 25 pts: Saline and 80 mg furosemide (30

minutes before angiography) Solomon R, et al. NEJM 1994

Effects of Saline, Mannitol, and

Furosemide

Effects of Saline, Mannitol, and Furosemide

• IV hydration with 0.45% saline before and after radiocontrast agents: the most effective means of preventing ARF in patients with CRI (with or without DM)

• Neither mannitol nor furosemide offered any additional benefit

Solomon R, et al. NEJM 1994

Renal-Dose Dopamine in ARF

Nail in the coffin– ANZICS Clinical trials Group

– 328 patients from 23 ICUs randomly assigned to receive low dose dopamine (2 mcg/kg/min) or placebo

– No difference in peak SCr, delta Cr, nedd for dialysis or death

Fenoldopam Use in the Prevention of ARF

• A selective D1 receptor agonist • Approved by FDA for the management of

hypertensive urgencies and emergencies• Significant peripheral vasodilatation,

decrease in systemic blood pressure, and increase in GFR by 33%, urine flow by 73%, and Na excretion by 48%

Elliott WJ, et al. Circulation 1990Shusterman NH, et al. Am J Med 1993

Fenoldopam Use in Contrast-Induced ARF

• Annapoorna S, et al. 2002:

Fenoldopam Controls

The incidence 4.7% 18.8%of ARF (p<0.001)

* Retrospective, non-randomized, historical controls

* Authors propose a protocol

Acetylcysteine (Mucomyst)

• A thiol-containing antioxidant• Used to treat a variety of pulmonary

diseases and acute acetaminophen poisoning

• Animals: ameliorates ischemic renal failure– Decreases oxidative stress– Nitric oxide– Cytokine inhibition

• Group I (n=41): acetylcysteine 600 mg po bid (on the day before and on the day of the procedure)+IV hydration with 0.45% saline (1 ml/kg/h for 12 hours before and 12 hours after CT scan)

• Group II (n=42): Placebo and 0.45% saline

Prophylactic Use of Acetylcysteine in Contrast-

induced ARF

N- Acetylcysteine Prevents Radiocontrast-Associated ARF

N- Acetylcysteine Prevents Radiocontrast-Associated ARF?

• No power calculations

• No analytical plan

• Reasonable power calculations = n > 1000

• INTERIM ANALYSIS

Atrial Natriuretic Peptide (ANP)

• Multicenter, prospective, randomized, double-blind, placebo-controlled trial of ANP in 256 patients with CRI

• Elective radiocontrast administration• Results: No benefit

Kurnik BRC, et al. AJKD, 1998

Sodium Bicarbonate to Prevent Acute Renal Failure

119 Patients with baseline sCr>1.1 who received radiocontrast and isotonic sodium bicarbonateor NaCl before and after the procedure (3mL/kg/h)

25% increase in sCr: 1 patient (NaHCO3) 8 patients (NaCl) p<0.02

Merten et al. JAMA 204

Prevention/Treatment of ARF

• No evidence for any benefit of diuretics• No evidence for any benefit of renal-dose

dopamine• No evidence for any benefit of Atrial

Natriuretic Peptide• Limited evidence for

– Intravenous hydration– Fenoldopam– Acetylcysteine

Renal Replacement Therapy in ARF

• Initiation

• Membrane

• ModalityContinuous vs. intermittent

• Quantification of delivered dose

The Uremic Syndrome

• Results from solute retention and malnutrition• Global deterioration in metabolic performance• Specific organ system dysfunction

Cardiovascular

Neurologic

Hematologic

Immunologic

Endocrinologic

Goals of Dialysis Therapy

Chronic Renal Failure

• Renal replacement• Amelioration of

uremic syndrome• Long term survival• Quality of life

Acute Renal Failure• Renal support• Improve organ system

function• Short term survival• Allow recovery of

renal function

Indications for Dialysis in ARF

• Electrolyte disturbances (Hyperkalemia)

• Fluid management

• Acute complications of uremia (pericarditis, bleeding)

• Severe acidosis

• Target BUN/Creatinine ?

Initiation of Dialysis in Acute Renal Failure

Fischer et al Kleinknecht et alSurg Gyn O 1966 KI 1972

Early Late Early Late

BUN (mg/dL) > 150 >200 >93 >164

Mortality (%) 51 77 27 42

Design Historical Historical Controls Controls

Does Hemodialysis Delay Recovery from ARF?

• Focal areas of fresh tubular necrosis in patients with prolonged ARF and on hemodialysis– Conger 1971

• Worsening BUN & Cr with delayed hypotension– Conger 1990 Seminars in Dialysis

Recurrent Hypotension Delays Recovery of Renal Function

0

1

2

3

4

0 2 4 6 8 10 12 14

Serum Creatinine mg/dL

Ctl ARF

Hypotension

Conger 1990

Renal Replacement Therapy in ARF

• Initiation

• Membrane

• ModalityContinuous vs. intermittent

• Quantification of delivered dose

CRRT vs IHD

• Efficiency in achieving solute, fluid and electrolyte balance

• Maintaining hemodynamic stability

• Effect on nutritional status

• Procedure-related complications

• Cost

• Impact on overall patient survival

Continuous Renal Replacement Therapy

Advantages• Hemodynamic

stability• More aggressive

nutrition• Gradual urea

removal• Cytokine removal

Disadvantages• Increased need for

anticoagulation• Patient immobility• Staff commitment

Renal Replacement Therapy in ARF

Inadequate data on when to initiate RRT in ARF

Biocompatible membranes provide survival advantage

The dialysis prescription and delivery are suboptimal

in ARF.