The metabolic clearance rate (MCR) of insulin was studied in 17 nondiabetic patients with advanced chronic renal failure (creatinine 479 +/- 15 mumol/L, glomerular filtration rate 14.6 +/- 2.9 mL/min) before and after 3 mo of a low-protein, low-phosphorus diet (LPD) providing daily per kilogram 0.3 protein of vegetal origin and 3-5 mg inorganic phosphorus. The energy supply (146 kJ.kg-1 x d-1) was furnished mainly by carbohydrates. The diet was supplemented with a mixture of essential amino acids and keto-analogues. The MCR of insulin was determined by using the euglycemic clamp technique. Before the diet the MCR of insulin was low (450 +/- 127 mL.min-1 x m-2) but increased significantly at the third month (568.8 +/- 148 mL.min-1 x m-2), reaching values close to the MCR of control subjects (630 +/- 135 mL.min-1 x m-2). Identical results have been described during hemodialysis of anephric patients, leading us to hypothesize that an LPD reduces the production of dialyzable factors that interfere with peripheral insulin metabolism.