BACKGROUND: High-protein diets are effective for weight reduction; however, little is known about the potential adverse renal effects of such diets. OBJECTIVE: The aim of our study was to compare the effect of a high-protein (HP) with a normal-protein (NP) diet on renal hemodynamics and selected clinical-chemical factors. DESIGN: We prospectively studied the effect of an HP diet (2.4 g x kg(-1) x d(-1)) with that of an NP diet (1.2 g x kg(-1) x d(-1)) on the glomerular filtration rate (assessed on the basis of sinistrin-an inulin analog-clearance) and renal plasma flow (para-aminohippuric acid clearance) by using the constant infusion technique. Filtration fraction and renal vascular resistance were calculated. Twenty-four healthy young men followed the 2 diet protocols for 7 d each in a crossover design. They were individually advised by a dietitian to achieve the planned protein intake by selecting normal foods under isocaloric conditions. Serum and urinary variables and renal hemodynamics were measured on day 7 of both diets. RESULTS: The glomerular filtration rate (NP: 125 +/- 5 mL/min; HP: 141 +/- 8 mL/min; P < 0.001) and filtration fraction (NP: 23 +/- 5%; HP: 28 +/- 5%; P < 0.05) increased significantly with the HP diet. Renal plasma flow was not significantly different between the HP (496 +/- 25 mL/min) and NP (507 +/- 18 mL/min) phases. Renal vascular resistance was not significantly different between the NP (94 +/- 6 mm Hg x mL(-1) x min(-1)) and HP (99 +/- 8 mm Hg x mL(-1) x min(-1)) phases. Blood urea nitrogen, serum uric acid, glucagon, natriuresis, urinary albumin, and urea excretion increased significantly with the HP diet. CONCLUSIONS: A short-term HP diet alters renal hemodynamics and renal excretion of uric acid, sodium, and albumin. More attention should be paid to the potential adverse renal effects of HP diets.