CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease

Abstract

Aims Patients with chronic kidney disease (CKD) pose a worldwide growing burden to health care systems due to accelerated atherosclerosis and subsequent high cardiovascular (CV) morbidity. Atherogenesis is prominently driven by monocytes and monocyte-derived macrophages. The expression of CD14 and CD16 characterizes three monocyte subsets: CD14++CD16-, CD14++CD16+, and CD14(+)CD16+ cells; the latter two are often denoted as 'proinflammatory' CD16+ monocytes. Despite an association between CD16+ monocyte counts and higher CV risk in cross-sectional cohorts, the prognostic impact of elevated CD16+ monocyte counts is poorly understood. Methods and resultsWe assessed monocyte heterogeneity using flow cytometry in 119 patients with non-dialysis CKD, who were prospectively followed for a median of 4.9 (inter-quartile range 4.85.0) years for the occurrence of CV events. In addition, we assessed expression of chemokine receptors on monocyte subsets. CD14++CD16+ monocyte were independently associated with CV events [hazard ratio (for an increase of 10 cells/μL) 1.26 (confidence interval: 1.041.52; P 0.018)] after adjustment for variables that significantly affected CD14++CD16+ cell counts at baseline. Across the spectrum of CKD, CD14++CD16+ monocytes selectively expressed CCR5. Conclusion We found that CD14++CD16+ monocytes were independently associated with CV events in non-dialysis CKD patients. Our results support the notion that CD16+ monocytes rather than CD16- monocytes are involved in human atherosclerosis. © 2010 The Author.