Haemodialysis-induced transient CD16+ monocytopenia and cardiovascular outcome

Background. Haemodialysis with bioincompatible membranes led to transient leukocyte activation and intradialytic leukopenia due to endothelial adherence. After the introduction of biocompatible membranes, only CD 161 (i.e. CD14(++)CD16(+) and CD14((+))CD16(+)) monocytes showed an impressive transient intra-dialytic decrease. Presently, it is unclear whether this CD16(+) monocyte drop is detrimental. We investigated whether a prominent intradialytic decrease of CD16(+) monocytes predicts future cardiovascular (CV) events. Methods. We measured leukocyte and monocyte subpopulations in 70 patients before and 10 min after haemodialysis initiation. Patients were stratified by their intra-dialytic CD14(++)CD16(+) monocyte drop (pre-defined major drop: decline of cell counts at 10 min to <50% of pre-dialytic values; pre-defined minor drop: decline to values >50% of pre-dialytic counts). Patients were followed up for 42 +/- 2 months; endpoints were CV events and death. Results. Patients with a minor CD14(++)CD16(+) monocyte drop had more CV events than patients with a major drop. In multivariate analysis, a minor CD14(++)CD16(+) monocyte drop was the strongest independent predictor of future CV events [hazard ratio 2.405 (95% CI 1.192-4.854)]. Conclusions. These data refute the assumption that a prominent intra-dialytic decrease of CD14(++)CD16(+) monocytes is detrimental. Instead, a minor cell drop could mirror CD14(++)CD16(+) monocyte dysfunction, with inadequate migratory reaction towards an immunologic stimulus posed by membrane and tubing contact.