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

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

Author information

1
Servicio de Nefrología, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Spanish Kidney Research Network (REDINREN), Madrid, Spain. Electronic address: marian.goicoechea@gmail.com.
2
Instituto de Investigación Sanitaria, Fundación Jiménez Díaz (IIS-FJD UAM), Madrid, Spain; Spanish Kidney Research Network (REDINREN), Madrid, Spain.
3
Servicio de Nefrología, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Spanish Kidney Research Network (REDINREN), Madrid, Spain.
4
Hospital Universitario La Princesa, Madrid, Spain.
5
Hospital Universitario Doce de Octubre, Madrid, Spain; Spanish Kidney Research Network (REDINREN), Madrid, Spain.
6
Hospital Universitario Fundación Alcorcón, Madrid, Spain; Spanish Kidney Research Network (REDINREN), Madrid, Spain.
7
Hospital Universitario Infanta Leonor, Madrid, Spain.

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

PMID:
28987723
DOI:
10.1016/j.plefa.2017.08.009
[Indexed for MEDLINE]

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