BACKGROUND: Thus far, there have been no controlled studies to examine optimal levels of energy provision in critically ill patients with acute renal failure (ARF) receiving artificial nutrition. METHODS: After a 24 h nitrogen-free regimen (20% dextrose), we assigned during an open-label, AB/BA-crossover-trial, 10 ARF patients receiving both total parenteral nutrition (TPN) and renal replacement therapy (seven males; mean age 72 years, range 60-83; mean APACHE II score 27.1, range 23-34, mechanical ventilation 8/10) to a lower calorie-TPN regimen (30 kcal/kg/day) and to a higher calorie-TPN regimen (40 kcal/kg/day), each for 3 days. Nitrogen intake was 0.25 g/kg/day for both regimens. We estimated nitrogen balance, protein catabolic rate and urea generation rate by urea kinetic methods based on both timed blood samples of serum urea and direct urea quantification from dialysis fluid. RESULTS: Two patients were excluded from the analysis (due to death and serum triglycerides above 5.1 mmol/l, respectively). Compared with the lower calorie-TPN, the higher calorie-TPN regimen did not improve estimated nitrogen balance [+1.55 g/day (95% confidence interval: -0.95 to +4.05, P = 0.18)], protein catabolic rate [-0.10 g/kg/day (-0.33 to +0.14, P = 0.35)], or urea generation rate [-1.3 mg/min (-5.2 to +2.7, P = 0.46)], whereas it increased serum triglycerides [+1.36 mmol/l (+0.53 to +2.19, P = 0.007)], glucose [+1.15 mmol/l (+0.07 to +2.24, P = 0.041)], insulin need [+20.4 U/day (+8.3 to +32.6, P = 0.006)] and nutritional fluid administration [+468 ml/day (+370 to +566, P<0.001)]. CONCLUSIONS: The present study, conducted in a small group of subjects, shows that in critically ill patients with ARF on a nitrogen intake of 0.25 g/kg/day, an energy provision of 40 kcal/kg/day does not improve nitrogen balance estimates compared with a 30 kcal/kg/day intake; instead, it may increase the risk of artificial nutrition-related side-effects.