Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Systemic inflammation is associated with exaggerated skeletal muscle protein catabolism in maintenance hemodialysis patients
Serpil M. Deger, … , Naji N. Abumrad, T. Alp Ikizler
Serpil M. Deger, … , Naji N. Abumrad, T. Alp Ikizler
Published November 16, 2017
Citation Information: JCI Insight. 2017;2(22):e95185. https://doi.org/10.1172/jci.insight.95185.
View: Text | PDF
Clinical Medicine Metabolism Nephrology

Systemic inflammation is associated with exaggerated skeletal muscle protein catabolism in maintenance hemodialysis patients

  • Text
  • PDF
Abstract

BACKGROUND. Systemic inflammation and muscle wasting are highly prevalent and coexist in patients on maintenance hemodialysis (MHD). We aimed to determine the effects of systemic inflammation on skeletal muscle protein metabolism in MHD patients. METHODS. Whole body and skeletal muscle protein turnover were assessed by stable isotope kinetic studies. We incorporated expressions of E1, E214K, E3αI, E3αII, MuRF-1, and atrogin-1 in skeletal muscle tissue from integrin β1 gene KO CKD mice models. RESULTS. Among 129 patients with mean (± SD) age 47 ± 12 years, 74% were African American, 73% were male, and 22% had diabetes mellitus. Median high-sensitivity C-reactive protein (hs-CRP) concentration was 13 (interquartile range 0.8, 33) mg/l. There were statistically significant associations between hs-CRP and forearm skeletal muscle protein synthesis, degradation, and net forearm skeletal muscle protein balance (P < 0.001 for all). The associations remained statistically significant after adjustment for clinical and demographic confounders, as well as in sensitivity analysis, excluding patients with diabetes mellitus. In attempting to identify potential mechanisms involved in this correlation, we show increased expressions of E1, E214K, E3αI, E3αII, MuRF-1, and atrogin-1 in skeletal muscle tissue obtained from an animal model of chronic kidney disease. CONCLUSION. These data suggest that systemic inflammation is a strong and independent determinant of skeletal muscle protein homeostasis in MHD patients, providing rationale for further studies using anticytokine therapies in patients with underlying systemic inflammation. FUNDING. This study was in part supported by NIH grants R01 DK45604 and 1K24 DK62849, the Clinical Translational Science Award UL1-TR000445 from the National Center for Advancing Translational Sciences, the Veterans Administration Merit Award I01 CX000414, the SatelliteHealth Normon Coplon Extramural Grant Program, and the FDA grant 000943.

Authors

Serpil M. Deger, Adriana M. Hung, Jorge L. Gamboa, Edward D. Siew, Charles D. Ellis, Cindy Booker, Feng Sha, Haiming Li, Aihua Bian, Thomas G. Stewart, Roy Zent, William E. Mitch, Naji N. Abumrad, T. Alp Ikizler

×

Figure 1

The diagram of metabolic study protocol.

Options: View larger image (or click on image) Download as PowerPoint
The diagram of metabolic study protocol.
The patients were admitted to G...
The patients were admitted to General Clinical Research Center the day before the study. They received a meal from bionutrition services after admission and remained in a fasting state for at least 10 hours prior to the initiation of the study. All metabolic studies were performed at least 24 hours after the most recent hemodialysis procedure. A primed constant infusion of L-(1-13C) leucine and L-(ring-2H5) phenylalanine was maintained throughout the metabolic study. Metabolic cart and plethysmography measurements were performed during the equilibration period. Blood and breath sampling were performed during the steady-state period.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts