Increased circulating endothelial apoptotic microparticle to endothelial progenitor cell ratio is associated with subsequent decline in glomerular filtration rate in hypertensive patients

PLoS One. 2013 Jul 12;8(7):e68644. doi: 10.1371/journal.pone.0068644. Print 2013.

Abstract

Background: Recent research indicates hypertensive patients with microalbuminuria have decreased endothelial progenitor cells (EPCs) and increased levels of endothelial apoptotic microparticles (EMP). However, whether these changes are related to a subsequent decline in glomerular filtration rate (GFR) remains unclear.

Methods and results: We enrolled totally 100 hypertensive out-patients with eGFR ≥ 30 mL/min/1.73 m(2). The mean annual rate of GFR decline (△GFR/y) was -1.49 ± 3.26 mL/min/1.73 m(2) per year during the follow-up period (34 ± 6 months). Flow cytometry was used to assess circulating EPC (CD34(+)/KDR(+)) and EMP levels (CD31(+)/annexin V(+)) in peripheral blood. The △GFR/y was correlated with the EMP to EPC ratio (r= -0.465, p<0.001), microalbuminuria (r= -0.329, p=0.001), and the Framingham risk score (r= -0.245, p=0.013). When we divided the patients into 4 groups according to the EMP to EPC ratio, there was an association between the EMP to EPC ratio and the ΔGFR/y (mean ΔGFR/y: 0.08 ± 3.04 vs. -0.50 ± 2.84 vs. -1.25 ± 2.49 vs. -4.42 ± 2.82, p<0.001). Multivariate analysis indicated that increased EMP to EPC ratio is an independent predictor of ΔeGFR/y.

Conclusions: An increased circulating EMP to EPC ratio is associated with subsequent decline in GFR in hypertensive patients, which suggests endothelial damage with reduced vascular repair capacity may contribute to further deterioration of renal function in patients with hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Count
  • Cell-Derived Microparticles / metabolism*
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Female
  • Flow Cytometry
  • Glomerular Filtration Rate*
  • Humans
  • Hypertension / pathology*
  • Hypertension / physiopathology*
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Stem Cells / metabolism*
  • Stem Cells / pathology

Grants and funding

This study was supported in part by research grants NSC 97-2314-B-075-039, NSC 98-2314-B-075-035, and UST-UCSD International Center of Excellence in Advanced Bio-engineering NSC-100-2911-I-009-101 from the National Science Council; VGH-V98B1-003 and VGH-V100E2-002 from Taipei Veterans General Hospital; and a grant from the Ministry of Education “Aim for the Top University” Plan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.