Protein metabolism in renal failure: abnormalities and possible mechanisms

Currently, we have only fragmentary knowledge about alterations of protein metabolism in renal failure, yet several coherent strands appear to be emerging. CRF is, in part, a state of malnutrition, as evidenced by abnormalities of body composition and alterations of both plasma and intracellular amino acid patterns. Superimposed upon this baseline are abnormalities specific to renal disease, changes in the concentration of certain amino acids, and the buildup of nitrogenous wastes and potential metabolic toxins, and the interaction of these toxins with hormones or within metabolic pathways. In acute renal failure, or when intercurrent illness is added to CRF, there is an intensification of the metabolic derangements and an acceleration of the normal catabolic response. Current research is directed at improving protein anabolism by limiting total nitrogen intake, while at the same time, providing supplemental amino or keto acids to restore and maintain nutritional state. Other approaches involve the provision of alternate pathways for nitrogen disposal and by direct stimulation of nitrogen anabolism through the administration of branched-chain amino acids or their keto acid analogues. All would agree that these modifications must be performed on a background of adequate caloric intake and careful patient monitoring. Given the complex nature of the problem, careful prospective controlled studies will be necessary before any hypothesis can be accepted. It is likely that additional improvements will require both a better understanding of the underlying metabolic defects and, probably, the combined application of several of the ideas previously noted.