Intradialytic hypertension and its association with endothelial cell dysfunction

Clin J Am Soc Nephrol. 2011 Aug;6(8):2016-24. doi: 10.2215/CJN.11351210. Epub 2011 Jul 14.

Abstract

Background and objectives: Intradialytic hypertension is associated with adverse outcomes, yet the mechanism is uncertain. Patients with intradialytic hypertension exhibit imbalances in endothelial-derived vasoregulators nitric oxide and endothelin-1, indirectly suggesting endothelial cell dysfunction. We hypothesized that intradialytic hypertension is associated in vivo with endothelial cell dysfunction, a novel predictor of adverse cardiovascular outcomes.

Design, settings, participants, & measurements: We performed a case-control cohort study including 25 hemodialysis (HD) subjects without (controls) and 25 with intradialytic hypertension (an increase in systolic BP pre- to postdialysis ≥10 mmHg ≥4/6 consecutive HD sessions). The primary outcome was peripheral blood endothelial progenitor cells (EPCs) assessed by aldehyde dehydrogenase activity (ALDH(br)) and cell surface marker expression (CD34(+)CD133(+)). We also assessed endothelial function by ultrasonographic measurement of brachial artery flow-mediated vasodilation (FMD) normalized for shear stress. Parametric and nonparametric t tests were used to compare EPCs, FMD, and BP.

Results: Baseline characteristics and comorbidities were similar between groups. Compared with controls, 2-week average predialysis systolic BP was lower among subjects with intradialytic hypertension (144.0 versus 155.5 mmHg), but postdialysis systolic BP was significantly higher (159.0 versus 128.1 mmHg). Endothelial cell function was impaired among subjects with intradialytic hypertension as measured by decreased median ALDH(br) cells and decreased CD34(+)CD133(+) cells (ALDH(br), 0.034% versus 0.053%; CD34(+)CD133(+), 0.033% versus 0.059%). FMD was lower among subjects with intradialytic hypertension (1.03% versus 1.67%).

Conclusions: Intradialytic hypertension is associated with endothelial cell dysfunction. We propose that endothelial cell dysfunction may partially explain the higher event rates observed in these patients.

Trial registration: ClinicalTrials.gov NCT00827775.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Aldehyde-Lyases / blood
  • Antigens, CD / blood
  • Antigens, CD34 / blood
  • Biomarkers / blood
  • Blood Pressure Monitoring, Ambulatory
  • Blood Pressure*
  • Case-Control Studies
  • Chi-Square Distribution
  • Endothelial Cells* / metabolism
  • Endothelium, Vascular / diagnostic imaging
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Female
  • Flow Cytometry
  • Glycoproteins / blood
  • Humans
  • Hypertension / blood
  • Hypertension / diagnostic imaging
  • Hypertension / etiology*
  • Hypertension / physiopathology
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / therapy*
  • Linear Models
  • Male
  • Middle Aged
  • Peptides / blood
  • Prospective Studies
  • Renal Dialysis / adverse effects*
  • Stem Cells* / metabolism
  • Texas
  • Ultrasonography, Doppler, Pulsed
  • Vasodilation*

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antigens, CD34
  • Biomarkers
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Aldehyde-Lyases
  • aldehyde decarbonylase

Associated data

  • ClinicalTrials.gov/NCT00827775