BACKGROUND: Haemodialysis with bioincompatible membranes led to transient leukocyte activation and intra-dialytic leukopenia due to endothelial adherence. After the introduction of biocompatible membranes, only CD16(+) (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 intra-dialytic 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.
BACKGROUND: Haemodialysis with bioincompatible membranes led to transient leukocyte activation and intra-dialytic leukopenia due to endothelial adherence. After the introduction of biocompatible membranes, only CD16(+) (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 intra-dialytic 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.
Authors: Gunnar H Heine; Alberto Ortiz; Ziad A Massy; Bengt Lindholm; Andrzej Wiecek; Alberto Martínez-Castelao; Adrian Covic; David Goldsmith; Gültekin Süleymanlar; Gérard M London; Gianfranco Parati; Rosa Sicari; Carmine Zoccali; Danilo Fliser Journal: Nat Rev Nephrol Date: 2012-03-13 Impact factor: 28.314