Dysregulated Handling of Dietary Protein and Muscle Protein Synthesis After Mixed-Meal Ingestion in Maintenance Hemodialysis Patients

Stephan van Vliet, Sarah K. Skinner, Joseph W. Beals, Brandon A. Pagni, Hsin Yu Fang, Alexander V. Ulanov, Zhong Li, Scott A. Paluska, Michael Mazzulla, Daniel W.D. West, Daniel R. Moore, Kenneth R. Wilund, Nicholas A. Burd

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Skeletal muscle loss is common in patients with renal failure who receive maintenance hemodialysis (MHD) therapy. Regular ingestion of protein-rich meals are recommended to help offset muscle protein loss in MHD patients, but little is known about the anabolic potential of this strategy. Methods: Eight MHD patients (age: 56 ± 5 years; body mass index [BMI]: 32 ± 2 kg/m2) and 8 nonuremic control subjects (age: 50 ± 2 years: BMI: 31 ± 1 kg/m2) received primed continuous L-[ring-2H5]phenylalanine and L-[1-13C]leucine infusions with blood and muscle biopsy sampling on a nondialysis day. Participants consumed a mixed meal (546 kcal; 20-g protein, 59-g carbohydrates, 26-g fat) with protein provided as L-[5,5,5-2H3]leucine-labeled eggs. Results: Circulating dietary amino acid availability was reduced in MHD patients (41 ± 5%) versus control subjects (61 ± 4%; P = 0.03). Basal muscle caspase-3 protein content was elevated (P = 0.03) and large neutral amino acid transporter 1 (LAT1) protein content was reduced (P = 0.02) in MHD patients versus control subjects. Basal muscle protein synthesis (MPS) was ∼2-fold higher in MHD patients (0.030 ± 0.005%/h) versus control subjects (0.014 ± 0.003%/h) (P = 0.01). Meal ingestion failed to increase MPS in MHD patients (absolute change from basal: 0.0003 ± 0.007%/h), but stimulated MPS in control subjects (0.009 ± 0.002%/h; P = 0.004). Conclusions: MHD patients demonstrated muscle anabolic resistance to meal ingestion. This blunted postprandial MPS response in MHD patients might be related to high basal MPS, which results in a stimulatory ceiling effect and/or reduced plasma dietary amino acid availability after mixed-meal ingestion.

Original languageEnglish (US)
Pages (from-to)1403-1415
Number of pages13
JournalKidney International Reports
Volume3
Issue number6
DOIs
StatePublished - Nov 2018

Keywords

  • chronic kidney disease
  • inflammation
  • insulin resistance
  • nutrition
  • protein digestion

ASJC Scopus subject areas

  • Ophthalmology
  • Nephrology

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