Urinary leukotriene E4 is associated with renal function but not with endothelial function in type 2 diabetes

Leukotrienes are inflammatory and vasoactive mediators implicated in endothelium-dependent relaxations and atherosclerosis. Urinary leukotriene E4 (U-LTE4) is a validated disease marker of asthma and increases also in diabetes and acute coronary syndromes. The aim of the present study was to evaluate the association of U-LTE4 and CRP with endothelial function. Urine samples were obtained from 30 subjects (80% males; median age 65) with type 2 diabetes of at least two years duration and a median glomerular filtration rate (eGFR) of 71 (14-129) mL/min. Reactive hyperemia index (RHI) was used as a measure of microvascular endothelial function, whereas macrovascular endothelial function was determined be means of flow-mediated dilatation of the brachial artery (FMD). Decreased renal function was associated with lower concentrations of U-LTE4. In addition, U-LTE4 was correlated with serum creatinine (R = -0.572; P = 0.001) and eGFR (R = 0.517; P = 0.0036). A stepwise multiple linear regression analysis identified eGFR as an independent predictor of U-LTE4 concentrations. In conclusion, the present results did not establish an association of U-LTE4 with endothelial dysfunction. However, eGFR was an independent predictor of U-LTE4, but not CRP, in this cohort, suggesting that GFR should be considered in biomarker studies of U-LTE4.