Format

Send to

Choose Destination
JCI Insight. 2017 Nov 16;2(22). pii: 95185. doi: 10.1172/jci.insight.95185. [Epub ahead of print]

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

Author information

1
Division of Nephrology, Vanderbilt University Medical Center (VUMC), Nashville, Tennessee, USA.
2
CSRD&D, Veterans Administration Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
3
Vanderbilt Center for Kidney Disease.
4
Division of Clinical Pharmacology, and.
5
Department of Biostatistics, VUMC, Nashville, Tennessee, USA.
6
Selzman Institute for Kidney Health, Baylor College of Medicine, Department of Medicine, Houston, Texas, USA.
7
Department of Surgery, VUMC, Nashville, Tennessee, USA.

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.

KEYWORDS:

Chronic kidney disease; Metabolism; Nephrology

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center