Increased platelet-monocyte aggregates and cardiovascular disease in end-stage renal failure patients

Abstract

Background: Atherosclerotic cardiovascular disease is a major cause of morbidity and mortality in patients with end-stage renal disease. This excess morbidity cannot be entirely explained by well-recognized conventional and novel risk factors alone, and occurs irrespective of dialysis modality. Recent evidence suggests that the activation of platelets and their interaction with circulating cells are important independent risk factors for atherosclerosis in non-uraemic patients. We therefore studied platelet activation and circulating platelet-leucocyte aggregates in stable patients without evidence of cardiovascular disease on continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis and investigated an association with cardiovascular events.

Methods: Immunofluorescent flow cytometry was used to measure the percentage of P-selectin- (CD62P) positive platelets, the percentage of platelet-neutrophil and platelet-monocyte aggregates, and the expression of the P-selectin ligand, P-selectin glycoprotein ligand-1 (PSGL-1, CD162) on leucocytes in haemodialysis and CAPD patients and normal controls. The platelet count and the mean platelet component (MPC, a measure of platelet activation) were determined on the ADVIATM 120 Haematology System (Bayer, NY).

Results: Platelet activation as assessed by MPC or CD62P expression was significantly increased in haemodialysis but not CAPD patients compared with controls. Circulating platelet-monocyte aggregates were significantly increased in parallel with a significant reduction in PSGL-1 expression on monocytes in both patient groups compared with normal controls. The presence of higher platelet-monocyte aggregates in dialysis patients was associated with increased cardiovascular events.

Conclusion: We describe increased platelet-monocyte aggregates with reduced leucocyte PSGL-1 expression in patients with end-stage renal disease irrespective of dialysis modality, associated with an increased risk of cardiovascular disease. These findings may suggest a novel mechanism by which accelerated atherosclerosis occurs in uraemic patients.