Markers of endothelial damage in patients with chronic kidney disease on hemodialysis

Am J Physiol Renal Physiol. 2017 Apr 1;312(4):F673-F681. doi: 10.1152/ajprenal.00013.2016. Epub 2017 Jan 11.

Abstract

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.

Keywords: cardiovascular disease; chronic kidney disease; diabetes mellitus; inflammation, hemodialysis; microvesicles.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiopoietin-1 / blood*
  • Angiopoietin-2 / blood*
  • Biomarkers / blood
  • Case-Control Studies
  • Cell-Derived Microparticles / metabolism*
  • Cell-Derived Microparticles / pathology
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / mortality
  • Diabetic Nephropathies / therapy*
  • Disease Progression
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Predictive Value of Tests
  • Prevalence
  • Renal Dialysis* / adverse effects
  • Renal Dialysis* / mortality
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / mortality
  • Renal Insufficiency, Chronic / therapy*
  • Spain / epidemiology
  • Time Factors
  • Treatment Outcome

Substances

  • ANGPT1 protein, human
  • ANGPT2 protein, human
  • Angiopoietin-1
  • Angiopoietin-2
  • Biomarkers
  • Inflammation Mediators