Omega-3 fatty acids inhibit the up-regulation of endothelial chemokines in maintenance hemodialysis patients

Nephrol Dial Transplant. 2015 Feb;30(2):266-74. doi: 10.1093/ndt/gfu283. Epub 2014 Sep 9.

Abstract

Background: Chronic systemic inflammation is common in patients with chronic kidney disease on dialysis (CKD5D) and has been considered a key mediator of the increased cardiovascular risk in this patient population. In this study, we tested the hypothesis that supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) will attenuate the systemic inflammatory process in CKD5D patients.

Methods: The design was a randomized, double-blinded, placebo controlled pilot trial (NCT00655525). Thirty-eight patients were randomly assigned in a 1 : 1 fashion to receive 2.9 g of eicosapentaenoic acid (C20:5, n-3) plus docosahexaenoic acid (C22:6, n-3) versus placebo for 12 weeks. The primary outcome was change in pro-inflammatory chemokines measured by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Secondary outcomes were changes in systemic inflammatory markers. Analysis of covariance was used to compare percent change from baseline to 12 weeks.

Results: Thirty-one patients completed 12 weeks and three patients completed 6 weeks of the study. Median age was 52 (interquartile range 45, 60) years, 74% were African-American and 79% were male. Supplementation of ω-3 PUFAs effectively decreased the LPS-induced PBMC expression of RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted) and MCP-1 (Monocyte Chemotactic Protein-1; unadjusted P = 0.04 and 0.06; adjusted for demographics P = 0.02 and 0.05, respectively). There was no significant effect of the intervention on serum inflammatory markers (C-reactive protein, interleukin-6 and procalcitonin).

Conclusions: The results of this pilot study suggest that supplementation of ω-3 PUFAs is beneficial in decreasing the levels of endothelial chemokines, RANTES and MCP-1. Studies of larger sample size and longer duration are required to further evaluate effects of ω-3 PUFAs on systemic markers of inflammation, other metabolic parameters and clinical outcomes, particularly cardiovascular outcomes in CKD5D patients.

Keywords: MCP-1; RANTES; end stage renal disease; inflammation; omega-3.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Calcitonin / blood
  • Calcitonin Gene-Related Peptide
  • Chemokines / metabolism*
  • Docosahexaenoic Acids / administration & dosage
  • Double-Blind Method
  • Eicosapentaenoic Acid / administration & dosage
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Fatty Acids, Omega-3 / administration & dosage*
  • Feasibility Studies
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Pilot Projects
  • Protein Precursors / blood
  • Renal Dialysis*
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / therapy*
  • Risk Factors
  • Up-Regulation

Substances

  • Biomarkers
  • CALCA protein, human
  • Chemokines
  • Fatty Acids, Omega-3
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Protein Precursors
  • Docosahexaenoic Acids
  • Calcitonin
  • C-Reactive Protein
  • Eicosapentaenoic Acid
  • Calcitonin Gene-Related Peptide