Mechanisms causing muscle wasting in uremia
Loss of muscle mass is common in patients with acute or chronic renal failure, but the mechanisms causing this problem are only beginning to be understood. One mechanism is that uremia blocks metabolic responses that act to maintain protein balance when anorexia reduces dietary protein. The adaptive metabolic responses include a sharp reduction in the degradation of essential amino acids and protein. In cultured myocytes, isolated muscles, and normal adults, acidification blocks these responses by stimulating the degradation of branched-chain amino acids and protein. The adverse effect of acidification requires glucocorticoids and involves stimulation of the activity of branched-chain ketoacid dehydrogenase and of the adenosine triphosphate-ubiquitin-proteasome-dependent proteolytic pathway. Understanding these mechanisms is important because the same pathways are activated in cancer, sepsis, burns, starvation, and muscle denervation. o 1996 by the National Kidney Foundation, Inc. B