The mechanism by which keto-acid-supplemented diets may retard the progression of renal failure is not known. We examined whether the protective effect of keto acids may be independent of a low nitrogen intake. Azotemic subtotally nephrectomized Sprague-Dawley rats were pair-fed a 30% casein diet supplemented with a 10% keto acid mixture (n = 10) or 10% cornstarch (n = 10) for 18 weeks. No differences were observed between the two groups of rats with regard to survival, weight gain, plasma urea, blood pressure, albuminuria, or, at the termination of the study, PAH and inulin clearances. Creatinine clearances, measured weekly during the study, were transiently higher in the keto acid group. There was no difference in the incidence or severity of segmental glomerulosclerosis or tubular atrophy in the two groups. These results indicate that the keto acid mixture used did not exert a protective effect against glomerular sclerosis and progressive albuminuria in azotemic rats fed high-protein diets.