BACKGROUND Patients with acute renal failure are in substantial negative nitrogen balance as a result of their extremely high protein catabolic rates. We prospectively evaluated a series of patients with acute renal failure managed with continuous venovenous hemofiltration to determine which nutritional and nonnutritional variables might influence protein catabolism and nitrogen balance. METHODS Forty consecutive patients (aged 52 +/- 20 years; mean +/- SD) were monitored for 357 treatment days (average treatment duration 8.9 +/- 8.6 days). All data (including nutritional regimen, laboratory values, APACHE II score, administered blood products, hemofiltration parameters, and medications) were collected daily. RESULTS For all patients, the mean normalized protein catabolic rate was 1.4 +/- 0.5 g/kg per day. The rate did not differ between those who received nutrition support and those who did not. The net nitrogen deficit was less in those patients receiving nutrition support (-6.0 +/- 5.2 vs -14.0 +/- 5.6 g N/d; p = .02). Using regression techniques (adjusted for the within-person correlation and the previous day's normalized protein catabolic rate), the level of protein and energy provision and the interaction between protein and energy provision were predictive of the normalized protein catabolic rate. Predicted values, using this equation, suggest that at low protein administration rates (< 1 g/kg per day), increasing energy provision may reduce the protein catabolism. However, at this level of protein provision, patients remain in negative nitrogen balance. At protein administration rates necessary to achieve nitrogen balance (approximately 1.5 to 1.8 g/kg per day), protein catabolism may increase. Providing relatively low levels of energy may diminish the magnitude of this increase. CONCLUSIONS These results suggest that the optimal nutritional regimen for patients with acute renal failure may require a high-protein (approximately 1.5 to 1.8 g/kg per day) and a relatively low-energy (approximately 25 to 35 kcal/kg per day) content.