Acidosis and glucocorticoids interact to provoke muscle protein and amino acid catabolism.

Malnutrition and a loss of lean body mass frequently complicate chronic renal failure. Muscle wasting in uremia is caused by increased protein degradation, decreased protein synthesis and increased branched-chain amino acid oxidation. Acidosis and glucocorticoids are pivotal in these pathophysiologic aberrations. When the acidosis of chronic renal failure is corrected by feeding bicarbonate, protein degradation and amino acid oxidation normalize. Likewise, if patients and animals with normal renal function are made acidotic, protein degradation and amino acid oxidation increase. In adrenalectomized, acidotic rats, proteolysis increases only when they are supplemented with physiologic concentrations of glucocorticoids, suggesting that glucocorticoids are necessary for increased proteolysis. Acidosis stimulates the ATP-dependent proteolytic process involving ubiquitin and the 26S proteasome. Thus, acidosis evokes a glucocorticoid-dependent catabolic response in muscle that can account for the protein wasting associated with uremia.