Increased Neutrophil Extracellular Trap Formation in Uremia Is Associated with Chronic Inflammation and Prevalent Coronary Artery Disease

Abstract

Background. Neutrophils are involved in the pathogenesis of atherosclerosis by neutrophil extracellular trap (NET) formation. We hypothesized that the NET formation of neutrophils might be changed in end-stage renal disease (ESRD) patients, explaining their higher incidence of coronary artery diseases (CAD). Method. A cross-sectional study was performed in 60 maintenance hemodialysis (MHD) patients, 30 age- and sex-matched healthy individuals (HV, negative control), and 30 patients with acute infection (positive control). Neutrophil activation and function were measured with reactive oxygen species (ROS) activity, degranulation, NET formation, and phenotypical changes. Result. Compared with HV, neutrophils extracted from MHD patients displayed significantly increased levels of basal NET formation, ROS production, and degranulation, suggesting spontaneous activation in uremia. Also, an increase in citrullinated histone H3 was detected in this group compared to the HV. And neutrophils from HV were normal CD16^bright/CD62L^bright cells; however, neutrophils from MHD were CD16^bright/CD62L^dim, similar to those from patients with acute infections. Interestingly, multivariate analyses identified the prevalent CAD and neutrophil counts as independent determinants of baseline NET formation (β = 0.323, p = 0.016 and β = 0.369, p = 0.006, resp.). Conclusions. Uremia-associated-increased NET formation may be a sign of increased burden of atherosclerosis.