Twice-told tales of metabolic acidosis, glucocorticoids, and protein wasting: What do results from rats tell us about patients with kidney disease?

Much has been learned from animal studies in chronic renal Failure that is germane to clinical studies because animal models parallel human responses. Such studies have affirmed that correction of metabolic acidosis has a fav orable effect on protein metabolism, nitrogen balance and growth. In the pr esence of metabolic acidosis, catabolism is increased in uremia. Glucocorti coids are involved in accelerating protein degradation in muscle, which res ults in loss of lean body mass, while a low insulin level appears to play a permissive role in accelerating increased catabolism. Cellular mechanisms mediating these changes include upregulation of the ubiquitin-proteasome pa thway and branched-chain ketoacid dehydrogenase enzyme activity in muscle. Many of these findings from rat studies have been confirmed in human studie s and have important clinical implications because correction of metabolic acidosis improves nutritional status and blunts the associated increase in protein catabolism.