Low dose aspirin increases 15-epi-lipoxin A4 levels in diabetic chronic kidney disease patients

Prostaglandins Leukot Essent Fatty Acids. 2017 Oct;125:8-13. doi: 10.1016/j.plefa.2017.08.009. Epub 2017 Aug 24.

Abstract

Background: Resolution of inflammation is regulated by endogenous lipid mediators, such as lipoxins and their epimers, including 15-epi-lipoxin A4 (15-epi-LXA4). However, there is no information on 15-epi-LXA4 and its in vivo regulation in chronic kidney disease (CKD) patients.

Study design: Open label randomized clinical trial.

Setting and participants: 50 participants with chronic kidney disease (CKD) stage 3 and 4 without prior cardiovascular disease (25 in the aspirin group and 25 in the standard group) followed for 46 months.

Intervention: Aspirin (100mg/day) or standard treatment.

Aim: To analyze the effect of aspirin on plasma 15-epi-LXA4 levels and inflammatory markers in CKD patients.

Results: Baseline plasma15-epi-LXA4 levels were lower in diabetic (1.22 ± 0.99ng/ml) than in non-diabetic CKD patients (2.05 ± 1.06ng/ml, p < 0.001) and inversely correlated with glycosylated hemoglobin levels (r = -0.303, p = 0.006). In multivariate analysis, diabetes was associated with lower 15-epi-LXA4 levels, adjusted for age, inflammatory markers and renal function (p = 0.005). In the whole study population, 15-epi-LXA4 levels tended to increase, but not significantly (p = 0.45), after twelve months on aspirin (from mean ± SD 1.84 ± 1.06 to 2.04 ± 0.75ng/ml) and decreased in the standard care group (1.60 ± 1.15 to 1.52 ± 0.68ng/ml, p = 0.04). The aspirin effect on 15-epi-LXA4 levels was more striking in diabetic patients, increasing from 0.94 ± 0.70 to 1.93 ± 0.74ng/ml, p = 0.017.

Conclusions: Diabetic patients with CKD have lower circulating 15-epi-LXA4 levels than non-diabetic CKD patients. Low dose aspirin for 12 months increased 15-epi-LXA4 levels in diabetic patients. Given its anti-inflammatory properties, this increase in 15-epi-LXA4 levels may contribute to the beneficial effects of low dose aspirin.

Keywords: 15-epi-lipoxin A4; Aspirin; Chronic kidney disease; Clinical trial; Inflammation; Lipoxins.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anti-Inflammatory Agents / therapeutic use
  • Aspirin / therapeutic use*
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Lipoxins / blood*
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / drug therapy*

Substances

  • Anti-Inflammatory Agents
  • Lipoxins
  • lipoxin A4
  • Aspirin