Amino Acid and protein kinetics in renal failure: an integrated approach.
Even apparently healthy patients on dialysis have significant loss of lean body mass. Patients with chronic renal failure without coexisting metabolic acidosis or inflammation have decreased protein turnover, with balanced reduction in protein synthesis and breakdown. However, regional and whole-body protein kinetic studies indicate that hemodialysis (HD) induces net increase in protein breakdown. Whole-body protein turnover studies show that HD is associated with decreased protein synthesis, but proteolysis is not increased. Muscle protein kinetics studies, however, identify enhanced muscle protein breakdown with inadequate compensatory increases in synthesis as the cause of the catabolism. Transmembrane amino acid-transport kinetics studies show that the outward transport is increased more than the inward transport of amino acids during HD. Altered intracellular amino acid transport kinetics and protein turnover during HD could be caused by the loss of amino acids in the dialysate or cytokine activation. Cytokines may be released from peripheral blood mononuclear cells and skeletal muscle during HD. Preliminary evidence indicates that intradialytic increase in cytokines activates the ubiquitin-proteasome pathway. An intradialytic increase in albumin and fibrinogen synthesis is facilitated by interleukin-6 and the constant supply of amino acids derived from skeletal muscle catabolism. Protein anabolism can be induced in end-stage renal disease patients by repletion of amino acids, and perhaps treatment with recombinant human insulin-like growth factor.
Raj
Dominic S C
DS
Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. draj@salud.unm.edu
Oladipo
Adeniyi
A
Lim
Victoria S
VS
D000596:Amino Acids / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D011506:Proteins / Q000378:metabolism*; D006435:Renal Dialysis
D000596:Amino Acids; D011506:Proteins