ACIDOSIS AND GLUCOCORTICOIDS INTERACT TO PROVOKE MUSCLE PROTEIN AND AMINO-ACID CATABOLISM

Malnutrition and a loss of lean body mass frequently complicate chroni c renal failure. Muscle wasting in uremia is caused by increased prote in degradation, decreased protein synthesis and increased branched-cha in amino acid oxidation. Acidosis and glucocorticoids are pivotal in t hese pathophysiologic aberrations. When the acidosis of chronic renal failure is corrected by feeding bicarbonate, protein degradation and a mino 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, proteoly sis increases only when they are supplemented with physiologic concent rations of glucocorticoids, suggesting that glucocorticoids are necess ary for increased proteolysis. Acidosis stimulates the ATP-dependent p roteolytic process involving ubiquitin and the 26S proteasome. Thus, a cidosis evokes a glucocorticoid-dependent catabolic response in muscle that can account for the protein wasting associated with uremia.