Low-protein diets (LPD) increase insulin-mediated glucose disposal in chronic renal failure (CRF), but the fate of the better utilized glucose and the effect on energy production rate are unknown. Using a two-step (1 and 5 mU x kg(-1) x min(-1)) euglycemic hyperinsulinemic clamp combined with indirect calorimetry, we studied the effects of a LPD (0.3 g x kg(-1) x day(-1), supplemented with essential amino acids and ketoanalogs) in six patients suffering from chronic renal failure. After three months of diet, no significant change was observed concerning glomerular filtration rate, body wt, or arterial pH. In the postabsorptive state, plasma glucose and insulin levels were significantly lower, and energy production rose from 15.72 +/- 0.48 to 17.16 +/- 0.67 Cal x kg(-1) x min(-1) (P < 0.05). Insulin-stimulated glucose oxidation (2.36 +/- 0.29 vs. 3.37 +/- 0.35 mg x kg(-1) x min(-1); P < 0.05 at first clamp step) and nonoxidative disposal (P < 0.05 at both clamp steps) increased after LPD. This confirms that LPD ameliorates insulin sensitivity in CRF, even for low plasma insulin concentrations. Since energy production rate is increased by LPD, the caloric intake should be increased when protein intake is restricted.