Hung Adriana M, Booker Cindy, Ellis Charles D, Siew Edward D, Graves Amy J, Shintani Ayumi, Abumrad Naji N, Himmelfarb Jonathan, Ikizler Talat Alp
CSR&D, Veterans Administration Tennessee Valley Healthcare System, Nashville, TN, USA Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA.
Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA.
Nephrol Dial Transplant. 2015 Feb;30(2):266-74. doi: 10.1093/ndt/gfu283. Epub 2014 Sep 9.
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.
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.
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).
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.
慢性全身炎症在接受透析的慢性肾脏病患者(CKD5D)中很常见,并且被认为是该患者群体心血管风险增加的关键介质。在本研究中,我们检验了补充ω-3多不饱和脂肪酸(ω-3 PUFAs)会减轻CKD5D患者全身炎症过程的假设。
本研究设计为一项随机、双盲、安慰剂对照的试验(NCT00655525)。38名患者以1:1的方式随机分组,分别接受2.9克二十碳五烯酸(C20:5,n-3)加二十二碳六烯酸(C22:6,n-3)或安慰剂,为期12周。主要结局是通过脂多糖(LPS)刺激的外周血单核细胞(PBMCs)测量的促炎趋化因子的变化。次要结局是全身炎症标志物的变化。采用协方差分析比较从基线到12周的百分比变化。
31名患者完成了12周的研究,3名患者完成了6周的研究。中位年龄为52岁(四分位间距45, 60),74%为非裔美国人,79%为男性。补充ω-3 PUFAs有效降低了LPS诱导的PBMC中RANTES(活化调节、正常T细胞表达和分泌)和MCP-1(单核细胞趋化蛋白-1)的表达(未校正P = 0.04和0.06;经人口统计学校正后P分别为0.02和0.05)。干预对血清炎症标志物(C反应蛋白、白细胞介素-6和降钙素原)无显著影响。
这项初步研究的结果表明,补充ω-3 PUFAs有助于降低内皮趋化因子RANTES和MCP-1的水平。需要进行更大样本量和更长时间的研究,以进一步评估ω-3 PUFAs对全身炎症标志物、其他代谢参数和临床结局的影响,特别是CKD5D患者的心血管结局。