acute renal failure
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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 - PowerPoint PPT PresentationTRANSCRIPT
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.