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In order to evaluate potential risk factors for the development of hospital-acquired acute renal failure, a case-control study was performed, comparing patients with hospital-acquired acute renal failure with control subjects matched on age, sex, hospital, service of admission, and baseline renal function. The same patients were then reanalyzed utilizing a cohort study design to investigate outcomes from this syndrome. The following elevated odds ratios (95 percent confidence interval) were found while simultaneously adjusting for possible confounding variables using logistic regression: volume depletion, 9.4 (2.1 to 42.8); aminoglycoside use, 5.6 (1.3 to 23.7); congestive heart failure 9.0 (2.1 to 38.9); radiocontrast exposure, 4.9 (1.2 to 19.7); and septic shock, approached infinity, p <0.0001. The effect of volume depletion was markedly accentuated in those with diabetes (odds ratio = 116.7) and decreased in those without diabetes (odds ratio = 1.9) (p <0.05). The risk from aminoglycoside use markedly increased with increasing age (p <0.002). Finally, the development of hospital-acquired acute renal failure was associated with a marked increase in the risk of dying—the relative risk (95 percent confidence interval) was 6.2 (2.6 to 14.9)—and a marked increase in length of stay, from a median of 13 days in control subjects to a median of 23 days in case subjects (p = 0.005). In conclusion, hospital-acquired acute renal failure is a serious illness. Attempts to prevent it should focus on proved risk factors.