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Acute renal failure is associated with significant morbidity and mortality rates. Need for dialysis is an independent risk factor for early mortality after complicated cardiac surgery. Human atrial natriuretic peptide (h-ANP) is a potent endogenous natriuretic and diuretic substance. Exogenous administration of h-ANP increases glomerular filtration rate and renal blood flow in clinical acute renal failure. We have studied the effects of h-ANP on renal outcome in ischemic acute renal failure.A prospective, double-blind, randomized, placebo-controlled study.Cardiothoracic intensive care units of two tertiary care centers.Sixty-one patients with normal preoperative renal function suffering from postcardiac surgical heart failure requiring significant inotropic and vasoactive support.The patients were randomized to receive a continuous infusion of either recombinant h-ANP (50 ng·kg−1·min−1) or placebo when serum creatinine increased by >50% from baseline. The treatment with h-ANP/placebo continued until serum creatinine decreased below the trigger value for inclusion or the patients fulfilled predefined criteria for dialysis.The primary outcome variable was dialysis on or before day 21 after the start of treatment. Secondary renal outcome variables were dialysis-free survival at day 21 and creatinine clearance. Twenty-nine patients were assigned h-ANP and 30 placebo. Six (21%) patients in the h-ANP group compared with 14 (47%) in the placebo group needed dialysis before or at day 21 (hazard ratio, 0.28; 95% confidence interval, 0.10–0.73; p = .009). Eight (28%) patients in the h-ANP group compared with 17 (57%) in the placebo group suffered from the combined end point dialysis or death before or at day 21 (hazard ratio, 0.35; 95% confidence interval, 0.14–0.82; p = .017). h-ANP improved creatinine clearance in contrast to placebo (p = .040).Infusion of h-ANP at a rate of 50 ng·kg−1·min−1 enhances renal excretory function, decreases the probability of dialysis, and improves dialysis-free survival in early, ischemic acute renal dysfunction after complicated cardiac surgery.