Acute Renal Failure

1. Acute Renal Failure Raymond C. Harris, M.D. Division of Nephrology

2. 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

3. Mortality in Acute Renal Failure * Nonrespiratory organ systems Chertow et al, Arch Intern Med, 1996

4. 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 hospitalization Group 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

5. Differential Diagnosis of Acute Renal Failure Acute Renal Failure Prerenal Intrinsic Renal Postrenal Vascular Glomerular Interstitial Tubular

6. 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)

7. Intrinsic Renal ARF • Prolonged prerenal state • Hypotension (surgery, bleeding) • Exposure to toxins (drugs, etc) • Drug sensitivity • Multisystem disease

8. 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

9. Physical Examination in Differential Diagnosis • Orthostatic hypotension, heart rate • Skin findings • Edema, ascites • Pelvic findings • Examination of optic fundi • Abdominal bruits

10. Urinary Electrolytes Fractional Excretion of Sodium (FENa): FENa=quantity of Na+ excreted = UNa x V = UNa x Pcr x100 quantity of Na+ filtered x100 PNa x (Ucr x V/Pcr) FENa< 1%= prerenal (usually) x100 PNa x Ucr

11. Urine Sediment • RBC casts GN, vasculitis • RTE cell casts ATN • Muddy brown casts ATN • WBCs, Eos AIN • Oxalate Ethylene Glycol • Bland Prerenal, Postrenal

12. 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

13. Prevention/Treatment of ARF • Intravenous hydration • Renal-dose dopamine • Fenoldopam • Acetylcysteine • Atrial Natriuretic Peptide • Endothelin receptor antagonists • Growth Factors

14. 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

15. Effects of Saline, Mannitol, and Furosemide

16. 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

17. 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

18. 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 1990 Shusterman NH, et al. Am J Med 1993

19. 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

20. 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

21. Prophylactic Use of Acetylcysteine in Contrast-induced ARF • 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

22. N- Acetylcysteine Prevents Radiocontrast-Associated ARF

23. N- Acetylcysteine Prevents Radiocontrast-Associated ARF? • No power calculations • No analytical plan • Reasonable power calculations = n > 1000 • INTERIM ANALYSIS

24. 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

25. Sodium Bicarbonate to Prevent Acute Renal Failure 119 Patients with baseline sCr>1.1 who received radiocontrast and isotonic sodium bicarbonate or 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

26. 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

27. Renal Replacement Therapy in ARF • Initiation • Membrane • Modality Continuous vs. intermittent • Quantification of delivered dose

28. The Uremic Syndrome • Results from solute retention and malnutrition • Global deterioration in metabolic performance • Specific organ system dysfunction Cardiovascular Neurologic Hematologic Immunologic Endocrinologic

29. 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 Goals of Dialysis Therapy

30. Indications for Dialysis in ARF • Electrolyte disturbances (Hyperkalemia) • Fluid management • Acute complications of uremia (pericarditis, bleeding) • Severe acidosis • Target BUN/Creatinine ?

31. Initiation of Dialysis in Acute Renal Failure Fischer et al Kleinknecht et al Surg Gyn O 1966 KI 1972 EarlyLateEarlyLate BUN (mg/dL) > 150 >200 >93 >164 Mortality (%) 51 77 27 42 Design Historical Historical Controls Controls

32. 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

33. Recurrent Hypotension Delays Recovery of Renal Function Hypotension Conger 1990

34. Renal Replacement Therapy in ARF • Initiation • Membrane • Modality Continuous vs. intermittent • Quantification of delivered dose

35. 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

36. Advantages Hemodynamic stability More aggressive nutrition Gradual urea removal Cytokine removal Disadvantages Increased need for anticoagulation Patient immobility Staff commitment Continuous Renal Replacement Therapy

37. 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.