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

Abstract

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.

Assessment of Endothelial and Microvascular Function in CKD: Older and Newer Techniques, Associated Risk Factors, and Relations with Outcomes

“…Similar observations were made in another study in 160 hemodi-alysis patients; EMP levels above the median were associated with increased all-cause mortality, after adjustment for diabetes and other traditional cardiovascular risk factors [138]. Despite the associations of EMPs with hard outcomes, the longitudinal EMP change was not associated with mortality [139].…”

New insight into the role of extracellular vesicles in kidney disease

“…Thus, leukocyte microvesicles transfer functional receptors to endothelial cell and promote kinin‐associated inflammation . Moreover, endothelial EVs levels, especially endothelial microparticles (EMPs) might also be useful biomarkers for chronic kidney disease (CKD) population and haemodialysis patients, which were associated with greater mortality …”

Hot off the Press: Endothelial Microparticles and Systemic Complement Activation in Patients with Chronic Kidney Disease

“…One hypothesis is that microparticles, sub-micrometer cellular vesicles that are released by cells under times of duress, may be the missing link in this schema. Indeed, microparticles have been long known to be elevated in patients with chronic kidney disease (CKD) 1 and patients on dialysis, as well as correlating with various other disease states such as diabetes 2 and hypertension.…”