Journal
JCI INSIGHT
Volume 2, Issue 22, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.95185
Keywords
-
Categories
Funding
- NIH [R01 DK45604, 1K24 DK62849]
- Clinical Translational Science from the National Center for Advancing Translational Sciences [UL1-TR000445]
- Veterans Administration Merit Award [I01 CX000414]
- SatelliteHealth Normon Coplon Extramural Grant Program
- FDA [000943]
Ask authors/readers for more resources
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, E3 alpha I, E3 alpha II, MuRF-1, and atrogin-1 in skeletal muscle tissue from integrin beta 1 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, E3 alpha I, E3 alpha II, 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available