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Acute renal failure is a complication in critically ill patients that has been associated with an excess risk of hospital mortality. Whether this reflects the severity of the disease or whether acute renal failure is an independent risk factor is unknown. The aim of this study was to analyze severity of illness and mortality in a group of critically ill patients with acute renal failure requiring renal replacement therapy in a number of Austrian intensive care units.Prospective, multicenter cohort study.A total of 17,126 patients admitted consecutively to 30 medical, surgical, and mixed intensive care units in Austria over a period of 2 yrs.Analyzed data included admission data, Simplified Acute Physiology Score, Logistic Organ Dysfunction system, Simplified Therapeutic Intervention Scoring System, length of intensive care unit stay, intensive care unit mortality, and hospital mortality. Of the admitted patients, 4.9% (n = 839) underwent renal replacement therapy because of acute renal failure (renal replacement therapy patients). These patients had a significantly higher hospital mortality (62.8% vs. 15.6%, p < .001), which remained significantly higher even when renal replacement therapy patients were matched with control subjects for age, severity of illness, and treatment center. Since univariate analysis demonstrated further intensity of treatment to be an additional predictor for outcome, a multivariate model including therapeutic interventions was developed. Five interventions were associated with nonsurvival (mechanical ventilation, single vasoactive medication, multiple vasoactive medication, cardiopulmonary resuscitation, and treatment of complicated metabolic acidosis/alkalosis). In contrast, the use of enteral nutrition predicted a favorable outcome.The results of our study suggest that acute renal failure in patients undergoing renal replacement therapy presents an excess risk of in-hospital death. This increased risk cannot be explained solely by a more pronounced severity of illness. Our results provide strong evidence that acute renal failure presents a specific and independent risk factor for poor prognosis.