Dietary supplementation of L-arginine ameliorates renal hypertrophy in rats fed a high-protein diet.

Ingestion of a high-protein diet or intravenous administration of amino acids is associated with an increase in glomerular filtration rate (GFR). It can also lead to renal hypertrophy, and, if sustained, may cause glomerular sclerosis. L-Arginine administration ameliorates the progression of renal disease in rats with subtotal nephrectomy and prevents the increase in GFR observed in rats with experimental diabetes. The present study examines the potential effect(s) of L-arginine administration (1%) in the drinking water on the renal hypertrophy that occurs in rats fed a high-protein diet for 1 month. Four groups of female Sprague-Dawley rats, six in each group, were studied (95 +/- 1 g). Groups 1 and 2 were fed a low-protein diet (12% casein, 0.504% L-arginine); Group 1 was given tap water, whereas Group 2 was given tap water supplemented with L-arginine. Groups 3 and 4 were fed a high-protein diet (40% casein, 1.68% L-arginine); Group 3 was given tap water, whereas Group 4 was given tap water supplemented with L-arginine. The rats had free access to food and water during the study period. The kidney weight and the kidney to body weight ratio of rats of Group 3 were significantly greater than in the other groups of rats. Renal hypertrophy was prevented in the rats of Group 4. The excretion of orotic acid in the urine, an index of L-arginine deficiency, was significantly greater in rats of Group 3 than in rats of Group 4. Thus, the renal hypertrophy that occurs in rats fed a high-protein diet was decreased in rats given L-arginine supplementation in the drinking water. This effect was associated with less excretion of orotic acid in the urine in rats given L-arginine. A relative deficiency of L-arginine may occur during high-protein feeding that may shunt nitrogen metabolism from the urea cycle to the orotic acid pathway.