Protein turnover and amino acid transport kinetics in end-stage renal disease

Raj, Dominic S.; Zager, Philip G.; Shah, Vallbh O.; Dominic, Elizabeth A.; Adeniyi, Oladipo; Blandon, Pedro; Wolfe, Robert R.; Ferrando, Arny A.

doi:10.1152/ajpendo.00352.2003

Cited by 52 publications

(42 citation statements)

References 49 publications

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“…Raj et al (16) studied intracellular amino acid transport kinetics using stable isotopes of three essential and two nonessential amino acidsnamely, phenylalanine, leucine, lysine, alanine, and glutamine-before and during HD. They found that during HD, there was increased amino acid efflux from the intracellular compartment into the vein as a result of increased protein breakdown.…”

Section: Three-compartmental Muscle Kineticsmentioning

confidence: 99%

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

Lim¹,

İkizler²,

Raj³

et al. 2005

Journal of the American Society of Nephrology

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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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Section: Three-compartmental Muscle Kineticsmentioning

confidence: 99%

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

Lim¹,

İkizler²,

Raj³

et al. 2005

Journal of the American Society of Nephrology

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“…Simultaneously, there is an increase in energy expenditure, which can last up to two hours after the dialysis session [6,7]. Other factors also contribute to the genesis of protein-energy malnutrition, such as: loss of amino acids during dialysis (4-8 grams per HD session on average, reaching up to 20 grams with highflux dialyzers), metabolic acidosis and low food intake [8,9].…”

Section: Research Articlementioning

confidence: 99%

Evaluation of the Impact of Nutritional Support on Quality of Life and Morbidity Indicators in Hemodialysis

Espirito¹,

Nestor²,

Rodrigues³

2018

J Nutri Med Diet Care

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“…Tracer infusion rates were increased by 10% during HDϩAA to maintain stable enrichment. Blood flow to the lower extremity was measured by dye dilution technique as described by our group previously (40).…”

Section: Subjectsmentioning

confidence: 99%

“…Muscle and whole body protein turnover studies have consistently demonstrated a balanced reduction in protein synthesis and degradation in stable ESRD patients (1,13,21,26). On the other hand, investigators unanimously agree that hemodialysis (HD) induces net protein catabolism (27,31,40). About 10 -12 g of amino acids are lost in the dialysate per HD session.…”

mentioning

confidence: 99%

“…Our group reported that amino acid depletion by HD promotes protein catabolism to maintain the plasma and intracellular amino acid concentrations (39). Our group also has shown that abnormal protein turnover in ESRD could be due to altered amino acid transport kinetics (40) and that interleukin-6 (IL-6) plays a key role in HD-induced muscle protein catabolism (42,43). Amino acid utilization for protein synthesis is impaired in patients with chronic renal failure (11).…”

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confidence: 99%

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Amino acid repletion does not decrease muscle protein catabolism during hemodialysis

Raj

Adeniyi²,

Dominic³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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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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Protein turnover and amino acid transport kinetics in end-stage renal disease

Cited by 52 publications

References 49 publications

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

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

Evaluation of the Impact of Nutritional Support on Quality of Life and Morbidity Indicators in Hemodialysis

Amino acid repletion does not decrease muscle protein catabolism during hemodialysis

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