The Association of Baseline and Longitudinal Change in Endothelial Microparticle Count with Mortality in Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with a unique milieu of vascular pathology, and effective biomarkers of active vascular damage are lacking. A candidate biomarker is the quantification of circulating endothelial microparticles (EMPs). This study observed baseline and longitudinal EMP change (δEMP) and established the association of these with all-cause mortality and cardiovascular events in CKD. METHOD: An observational study in adults with CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2). EMPs were quantified by flow cytometry of platelet poor plasma in 2 samples 12 months apart and categorised as EMP if AnnexinV+/CD31+/CD42b- EMPs were compared between primary renal diagnoses, and correlations between EMP/δEMP and other parameters made. Adjusted hazard ratios (HRs) for time to all-cause mortality and cardiovascular events were calculated for log-transformed EMP and δEMP using a Cox proportional hazard model. RESULTS: There were 123 patients (age 63 ± 11 years, systolic blood pressure 135 ± 18 mm Hg, eGFR 32 ± 16 mL/min/1.73 m2). The median baseline EMP count was 144/µL (range 10-714/µL). EMPs were numerically the highest in autosomal dominant polycystic kidney disease (253 [41-610]). An increase in urine protein:creatinine ratio was associated with an increase in EMP (co-efficient 0.21, p = 0.02). The adjusted HR for all-cause mortality for EMP was 8.20 (1.67-40.2, p = 0.01) and for δEMP was 2.69 (0.04-165, p = 0.64). There was no association between EMP or δEMP and cardiovascular events. CONCLUSION: Although EMP count was a significant marker of mortality risk, longitudinal change was not. This may reflect disease-specific EMP behaviour and the limitation of EMP as a generalised biomarker in CKD.