title: Omega-3 fatty acids inhibit the up-regulation of endothelial chemokines in maintenance hemodialysis patients.
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.
authors.affiliation: CSR&D, Veterans Administration Tennessee Valley Healthcare System, Nashville, TN, USA Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Hung
authors.affiliation: Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Booker
authors.affiliation: Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Ellis
authors.affiliation: CSR&D, Veterans Administration Tennessee Valley Healthcare System, Nashville, TN, USA Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Siew
authors.affiliation: Division of Biostatistics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Graves
authors.affiliation: Division of Biostatistics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Shintani
authors.affiliation: Department of Surgery, Vanderbilt University, Nashville, TN, USA.
authors.forename: Naji N
authors.initials: NN
authors.lastname: Abumrad
authors.affiliation: Kidney Research Institute, University of Washington, Seattle, WA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Himmelfarb
authors.affiliation: CSR&D, Veterans Administration Tennessee Valley Healthcare System, Nashville, TN, USA Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Talat Alp
authors.initials: TA
authors.lastname: Ikizler
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D018925:Chemokines / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011498:Protein Precursors / Q000097:blood; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000628:therapy*; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D018925:Chemokines; D015525:Fatty Acids, Omega-3; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D011498:Protein Precursors; D004281:Docosahexaenoic Acids; D002116:Calcitonin; D002097:C-Reactive Protein; D015118:Eicosapentaenoic Acid; D015740:Calcitonin Gene-Related Peptide
keywords: MCP-1; RANTES; end stage renal disease; inflammation; omega-3