Does Hemodialysis Increase Protein Breakdown? Dissociation between Whole-Body Amino Acid Turnover and Regional Muscle Kinetics

Abstract

Hemodialysis (HD) is a protein catabolic procedure. Whole-body amino acid turnover studies identify dialysate amino acid loss and reduced protein synthesis as the catabolic events; proteolysis is not increased. Regional amino acid kinetics, however, document enhanced muscle protein breakdown as the cause of the catabolism; muscle protein synthesis also increased but to a lesser magnitude than the increment in protein breakdown. This discordance between whole-body and regional kinetics is best explained by the contrasting physiology between the muscle and the liver. During HD, muscle releases amino acids, which then are taken up by the liver for de novo protein synthesis. There seems to be a somatic to visceral recycling of amino acids. Evidence supporting this concept includes the increased fractional synthesis of albumin and fibrinogen during HD. It should be emphasized that region-or organ-specific kinetics vary, and whole-body turnover is a composite of all of the visceral and somatic compartments taken together. Reduced whole-body protein synthesis may be a compensatory adaptation to dialysate amino acid loss with a consequent reduction in plasma amino acid concentration. Notwithstanding the protein catabolic nature of HD, evidence is accumulating that intradialytic nutritional supplementation may blunt its catabolic effect. U ntil recently, uremia was believed to be a protein catabolic state. This view is no longer tenable because numerous whole-body amino acid turnover studies have unequivocally revealed that there is no excess protein catabolism in the chronic renal failure population in the absence of acidosis and/or concomitant illnesses (1). Uremic patients respond to low-protein diets with appropriate downregulation of whole-body proteolysis (2,3). Peritoneal dialysis is protein catabolic primarily because of protein and amino acid losses through the peritoneal effluent (4). The remaining unsettled issue is whether hemodialysis (HD) induces protein catabolism and, if it does, by what mechanism. There are theoretical reasons to believe that HD can augment protein catabolism. These include amino acid loss to the dialysate and cytokinemediated proteolysis as a result of exposure to bio-incompatible membrane and endotoxin-contaminated dialysate, but to date, investigation of protein metabolism using different techniques has yielded conflicting results. J Am Soc Nephrol Protein Metabolism during HD: A Review of the LiteratureThis article reviews the available literature of protein metabolism during HD and proposes a unifying hypothesis to explain the discordant results and diverging conclusions. The work cited in this review is categorized according to the technique used. Nitrogen Balance Combined with Urea KineticsThe seminal findings of Borah et al. (5) that nitrogen balance is always more negative or less positive, depending on the intake, on dialysis days compared with nondialysis days greatly influenced the belief that HD is a protein catabolic procedure. Lim et al. (6) also reported that nitrogen ou...

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