title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Population Health, University of Manchester, Manchester, UK.
authors.forename: Darren
authors.initials: D
authors.lastname: Green
authors.forename: Sarah
authors.initials: S
authors.lastname: Skeoch
authors.forename: M Yvonne
authors.initials: MY
authors.lastname: Alexander
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kalra
authors.forename: Ben
authors.initials: B
authors.lastname: Parker
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D055252:Cell-Derived Microparticles / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005919:Glomerular Filtration Rate; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology; D012307:Risk Factors; D016019:Survival Analysis; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D015415:Biomarkers