Mechanisms causing muscle loss in chronic renal failure.

The loss of lean body mass in uremia is associated with excessive morbidity and mortality. A potential mechanism causing protein catabolism is that uremia overcomes critical metabolic responses required to maintain protein balance whenever dietary protein is limited. These responses include reduced oxidation of essential amino acids, which improves the efficiency of protein utilization and a reduction in protein degradation. We find that metabolic acidosis stimulates both amino acid oxidation and protein degradation in muscle and thus could overcome the adaptive responses. The molecular mechanisms stimulating catabolism involve glucocorticoids and includes increased mRNAs of components of catabolic pathways. Studies in patients have confirmed that acidosis causes catabolism in chronic renal failure. Thus, we recommend that patients with metabolic acidosis receive an adequate diet and sufficient alkali to correct acidosis.