. Protein turnover and amino acid transport kinetics in end-stage renal disease. Am J Physiol Endocrinol Metab 286: E136-E143, 2004. First published September 16, 2003 10.1152/ ajpendo.00352.2003.-Protein and amino acid metabolism is abnormal in end-stage renal disease (ESRD). Protein turnover is influenced by transmembrane amino acid transport. The effect of ESRD and hemodialysis (HD) on intracellular amino acid transport kinetics is unknown. We studied intracellular amino acid transport kinetics and protein turnover by use of stable isotopes of phenylalanine, leucine, lysine, alanine, and glutamine before and during HD in six ESRD patients. Data obtained from amino acid concentrations and enrichment in the artery, vein, and muscle compartments were used to calculate intracellular amino acid transport and muscle protein synthesis and catabolism. Fractional muscle protein synthesis (FSR) was estimated by the precursor product approach. Despite a significant decrease in the plasma concentrations of amino acids in the artery and vein during HD, the intracellular concentrations remained stable. Outward transport of the amino acids was significantly higher than the inward transport during HD. FSR increased during HD (0.0521 Ϯ 0.0043 vs. 0.0772 Ϯ 0.0055%/h, P Ͻ 0.01). Results derived from compartmental modeling indicated that both protein synthesis (118.3 Ϯ 20.6 vs. 146.5 Ϯ 20.6 nmol⅐min Ϫ1 ⅐100 ml leg Ϫ1 , P Ͻ 0.01) and catabolism (119.8 Ϯ 18.0 vs. 174.0 Ϯ 14.2 nmol⅐min Ϫ1 ⅐100 ml leg Ϫ1 , P Ͻ 0.01) increased during HD. However, the intradialytic increase in catabolism exceeded that of synthesis (57.8 Ϯ 13.8 vs. 28.0 Ϯ 8.5%, P Ͻ 0.05). Thus HD alters amino acid transport kinetics and increases protein turnover, with net increase in protein catabolism. protein synthesis; protein catabolism; amino acid metabolism; hemodialysis LOSS OF LEAN BODY MASS is common in patients with end-stage renal disease (ESRD) (47). The etiology of uremic cachexia remains elusive and controversial. However, malnutrition is one of the most important predictors of increased mortality and morbidity. Accumulation of uremic toxins, anorexia, metabolic acidosis, loss of metabolizing renal tissue, perturbations in the production of or responsiveness to catabolic and anabolic hormones, and activation of cytokines act in concert to contribute to the muscle wasting in uremia (4, 5). A healthy adult synthesizes and degrades ϳ200 g of tissue protein every day; consequently, even a small but sustained change in protein balance will have a major impact on lean body mass (44). Augmented protein catabolism and/or decreased protein synthesis in ESRD could be the cause of uremic cachexia. A number of investigators have observed that protein turnover is abnormal in ESRD. Metabolic acidosis that accompanies chronic renal failure (CRF) is known to promote protein catabolism (3, 39). However, the effect of uremia per se on protein turnover independent of metabolic acidosis has not been rigorously studied. Also, the effect of hemodialysis on protein turnover r...

Intradialytic protein catabolism is attributed to loss of amino acids in the dialysate. We investigated the effect of amino acid infusion during hemodialysis (HD) on muscle protein turnover and amino acid transport kinetics by using stable isotopes of phenylalanine, leucine, and lysine in eight patients with end-stage renal disease (ESRD). Subjects were studied at baseline (pre-HD), 2 h of HD without amino acid infusion (HD-O), and 2 h of HD with amino acid infusion (HD+AA). Amino acid depletion during HD-O augmented the outward transport of amino acids from muscle into the vein. Increased delivery of amino acids to the leg during HD+AA facilitated the transport of amino acids from the artery into the intracellular compartment. Increase in muscle protein breakdown was more than the increase in synthesis during HD-O (46.7 vs. 22.3%, P < 0.001). Net balance (nmol·min−1·100 ml −1) was more negative during HD-O compared with pre-HD (−33.7 ± 1.5 vs. −6.0 ± 2.3, P < 0.001). Despite an abundant supply of amino acids, the net balance (−16.9 ± 1.8) did not switch from net release to net uptake. HD+AA induced a proportional increase in muscle protein synthesis and catabolism. Branched chain amino acid catabolism increased significantly from baseline during HD-O and did not decrease during HD+AA. Protein synthesis efficiency, the fraction of amino acid in the intracellular pool that is utilized for muscle protein synthesis decreased from 42.1% pre-HD to 33.7 and 32.6% during HD-O and HD+AA, respectively ( P < 0.01). Thus amino acid repletion during HD increased muscle protein synthesis but did not decrease muscle protein breakdown.

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Hypoalbuminemia is associated with increased risk of HD access infection. Treatment of HD access infection with antibiotics alone is associated with increased risk of death.