Administration of IL-1ra improves adiponectin levels in chronic hemodialysis patients
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Adiponectin, an adipose tissue derived hormone, is known to have insulin-sensitizing, anti-inflammatory, and anti-atherogenic properties in the general population. Adiponectin secretion is suppressed by systemic inflammation, a highly prevalent condition in maintenance hemodialysis (MHD) patients. We evaluated whether short-term administration of interleukin 1 receptor antagonist (IL-1ra) improves adiponectin levels and insulin sensitivity in MHD patients.
Ad hoc analysis was performed on a pilot randomized placebo-controlled trial of the administration of IL-1ra in chronically inflamed MHD patients. Twenty-two patients were randomly assigned to receive 100 mg of IL-1ra or placebo (1:1) for 4 weeks, and 14 completed the trial. ANCOVA was used to compare percent change from baseline to 4 weeks. The primary outcome was percent change in adiponectin and the secondary outcomes were changes in leptin, homeostatic model assessment of insulin resistance (HOMA-IR) and the leptin-to-adiponectin ratio (LAR).
Patients’ mean age was 49 ± 13 years, and 71 % were males. At baseline, the median values for adiponectin, leptin, LAR and HOMA-IR were 11.5 μg/ml [interquartile range (IQR) 9, 28.5], 17.8 ng/ml (3.9, 50.0), 2.20 (0.13, 3.98), and 2.8 (2.0, 3.6), respectively. IL-1ra administration resulted in a mean percent increase in serum adiponectin of 22 % vs. 14 % decrease in the placebo arm (p = 0.003). Leptin, LAR or HOMA-IR levels did not change in either arm.
Short-term administration of IL-1ra significantly increased adiponectin levels among prevalent MHD patients. The intervention did not impact insulin sensitivity parameters. Studies of longer duration and larger sample size are needed to further evaluate the potential effect of anti-inflammatory interventions on metabolic markers and insulin sensitivity in MHD patients.
KeywordsAnakinra Interleukin 1-ra Adiponectin Dialysis Insulin resistance
This study was supported in part by grants R21 DK077373, K24 DK062849 and the Vanderbilt Diabetes Research and Training Center grant P30 DK020593 from the National Institute of Diabetes and Digestive and Kidney Diseases, Clinical Translational Science Award UL1-TR000445 from the National Center for Advancing Translational Sciences, and a National Kidney Foundation Young Investigator Award. A.H. was supported in full by VA Career Development Award 2-031-09S from the CSR&D. C.L was partly supported by an International Society of Nephrology Fellowship grant. Study drug and matching placebo were kindly provided by Amgen (Thousand Oaks, CA, USA).
Conflict of interest
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