The effect of hemodialysis on protein metabolism. A leucine kinetic study.

Lim, Victoria S.; Bier, Dennis M.; Flanigan, Michael J.; Sum-Ping, Sam T.

doi:10.1172/jci116477

Cited by 107 publications

(53 citation statements)

References 26 publications

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“…Our study further underscores that, despite the catabolic nature of the hemodialysis procedure (25,26), patients undergoing maintenance hemodialysis can achieve anabolism when given sufficient protein supply and when adequate insulin is present. The recent work of Pupim et al (27) showing increased protein synthesis and net protein balance with intradialytic parenteral nutrition supports this notion.…”

Section: Discussionsupporting

confidence: 52%

Insulin Is Protein-Anabolic in Chronic Renal Failure Patients

Lim¹,

Yarasheski²,

Crowley³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. To examine the protein anabolic actions of insulin in chronic renal failure, the authors measured four sets of whole body leucine fluxes during insulin alone and insulin with amino acid infusion in nine uremic patients before hemodialysis (B-HD). Seven were restudied 8 wk after initiation of maintenance hemodialysis (HD). Six normal subjects served as control (N). All values ( mol/kg/h, mean Ϯ SEM) are presented in the sequence of B-HD, HD, and N, and only P Ͻ 0.05 are listed. During Flux 1 (baseline), D (leucine release from body protein degradation) were 114 Ϯ 7, 126 Ϯ 4, and 116 Ϯ 6, respectively. C (leucine oxidation rates) were 18 Ϯ 2, 17 Ϯ 2, and 21 Ϯ 3, respectively. S (leucine disappearance into body protein [index of protein synthesis]) were 96 Ϯ 6, 107 Ϯ 4, and 94 Ϯ 4, respectively, and balances (net leucine flux into protein [values were negative during fasting]) were Ϫ18 Ϯ 2, Ϫ17 Ϯ 2, and Ϫ21 Ϯ 3, respectively. During Flux 2 (low-dose insulin infusion), D were 89 Ϯ 3, 98 Ϯ 6, and 94 Ϯ 5, respectively; C were 12 Ϯ 1, 11 Ϯ 2, and 18 Ϯ 1, respectively (P ϭ 0.02); S were 77 Ϯ 4, 87 Ϯ 5, and 76 Ϯ 5, respectively, and balances were Ϫ12 Ϯ 1, Ϫ11 Ϯ 2, and Ϫ18 Ϯ 1, respectively (P ϭ 0.02). During Flux 3 (high-dose insulin infusion): D were 77 Ϯ 3, 82 Ϯ 7, and 84 Ϯ 5, respectively; C were 9 Ϯ 1, 8 Ϯ 1, and 14 Ϯ 1, respectively (P ϭ 0.005); S were 68 Ϯ 4, 74 Ϯ 6, and 70 Ϯ 5, respectively, and balances were Ϫ9 Ϯ 1, Ϫ8 Ϯ 1, and Ϫ14 Ϯ 1, respectively (P ϭ 0.005). In Flux 4 (insulin infused with amino acids): D were 73 Ϯ 3, 107 Ϯ 18, and 85 Ϯ 7, respectively; C were 35 Ϯ 4, 29 Ϯ 5, and 39 Ϯ 3, respectively; S were 105 Ϯ 5, 145 Ϯ 15, and 113 Ϯ 6, respectively (P ϭ 0.02), and balances were 32 Ϯ 4, 38 Ϯ 5, and 27 Ϯ 3, respectively. These data show that B-HD and HD patients were as sensitive as normal subjects to the protein anabolic actions of insulin. Insulin alone reduced proteolysis and leucine oxidation, and insulin given with amino acids increased net protein synthesis.There is a prevailing view in the nephrology community that uremia is an insulin-resistant state. In reviews relating malnutrition to chronic renal failure (CRF), insulin resistance is invariably mentioned as a potential cause for the increase in protein catabolism (1-3). This perception is derived partially from the well-described phenomenon of impaired non-oxidative glucose disposal in uremic patients (4,5) and partially from findings of increased release and impaired incorporation of amino acids from and into tissue during insulin treatment in acute and chronic uremic rat models (6,7). Despite this general belief, there are few papers addressing insulin action on protein metabolism in CRF patients (8 -13). Whether uremia imparts insulin resistance and whether maintenance hemodialysis alters insulin sensitivity with regard to protein metabolism in humans is uncertain. Malnutrition is a pervasive problem in CRF patients (14 -16); it is therefore important to investigate whether insulin retains its anabolic function in this population.In ...

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Section: Discussionsupporting

confidence: 52%

Insulin Is Protein-Anabolic in Chronic Renal Failure Patients

Lim¹,

Yarasheski²,

Crowley³

et al. 2003

Journal of the American Society of Nephrology

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“…Lim et al (11) were some of the earliest investigators to quantify whole-body protein turnover during HD in ESRD patients using primed-constant infusion of 13 C leucine. Because Gutierrez's paper identified peak protein catabolism Ͼ3 h after dialysis, they studied leucine flux 2 h before and 4 h after dialysis and shortened the dialysis session to 2.5 hours to avoid isotope recycling.…”

Section: In Vivo Whole-body Amino Acid Turnover 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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“…The comparable values were 0.45 and 0.48, respectively, for the post-hemodialysis phase. For leucine oxidation we used values of 0.77 and 0.85, respectively, for the postabsorptive and fed periods, as obtained previously in healthy subjects (16); these values are similar to those applied by Lim et al (25) in studies of leucine kinetics in ESRD patients.…”

Section: Figurementioning

confidence: 99%