Leucine and protein metabolism in rats with chronic renal insufficiency

The aim of this study was to evaluate the effect of chronic uremia induced by 5/6 nephrectomy (5/6NX) on changes in protein and branched-chain amino a cid (BCAA; valine, leucine and isoleucine) metabolism. The control group co nsisted of sham operated rats. Twenty eight weeks after surgery the paramet ers of protein and amino acid metabolism were evaluated using a primed cons tant intravenous infusion of L-[1-C-14]leucine. A drop in BCAA levels and a significant increase in urea, creatinine and cholesterol were observed in plasma of all 5/6NX rats. However, severe uremia with acidosis developed on ly in one third of rats with 5/6NX. In 5/6NX rats with acidosis significant increases in proteolysis, leucine oxidation, leucine oxidized fraction, an d leucine clearance were observed in comparison with the control group and rats with 5/6NX without acidosis. In addition, in 5/6NX rats with acidosis a significant decrease in valine concentration in gastrocnemius muscle was found. We conclude that marked activation of proteolysis occurs in severe c hronic renal failure and is probably caused by metabolic changes related to acidosis development.