Probing the mechanisms of intradialytic hypertension: a pilot study targeting endothelial cell dysfunction

Clin J Am Soc Nephrol. 2012 Aug;7(8):1300-9. doi: 10.2215/CJN.10010911. Epub 2012 Jun 14.

Abstract

Background and objectives: Intradialytic hypertension may be caused by an impaired endothelial cell response to hemodialysis. Carvedilol has been shown to improve endothelial cell function in vivo and to block endothelin-1 release in vitro. This study hypothesized that carvedilol would improve endothelial cell function and reduce the occurrence of intradialytic hypertension.

Design, setting, participants, & measurements: A prospective 12-week pilot study of carvedilol titrated to 50 mg twice daily was performed among 25 hemodialysis participants with intradialytic hypertension. Each patient served as his or her own control. Paired tests were used to analyze changes in BP and endothelial cell function--assessed by flow-mediated vasodilation, endothelial progenitor cells (aldehyde dehydrogenase bright activity and CD34(+)CD133(+)), asymmetric dimethylarginine, and endothelin-1--from baseline to study end.

Results: Flow-mediated vasodilation was significantly improved with carvedilol (from 1.03% to 1.40%, P=0.02). There was no significant change in endothelial progenitor cells, endothelin-1, or asymmetric dimethylarginine. Although prehemodialysis systolic BP was unchanged (144-146 mmHg, P=0.5), posthemodialysis systolic BP, 44-hour ambulatory systolic BP, and the frequency of intradialytic hypertension decreased with carvedilol (159-142 mmHg, P<0.001; 155-148 mmHg, P=0.05; and 77% [4.6 of 6] to 28% [1.7 of 6], P<0.001, respectively).

Conclusions: Among hemodialysis participants with intradialytic hypertension, targeting endothelial cell dysfunction with carvedilol was associated with modest improvements in endothelial function, improved intradialytic and interdialytic BP, and reduced frequency of intradialytic hypertension. Randomized controlled trials are required to confirm these findings.

Trial registration: ClinicalTrials.gov NCT00827775.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Aldehyde Dehydrogenase / metabolism
  • Antigens, CD / metabolism
  • Antigens, CD34 / metabolism
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Arginine / analogs & derivatives
  • Arginine / metabolism
  • Biomarkers / metabolism
  • Blood Pressure / drug effects
  • Blood Pressure Monitoring, Ambulatory
  • Body Weight / drug effects
  • Carbazoles / adverse effects
  • Carbazoles / therapeutic use*
  • Carvedilol
  • Endothelin-1 / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Female
  • Glycoproteins / metabolism
  • Humans
  • Hypertension / etiology
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Hypertension / prevention & control*
  • Male
  • Middle Aged
  • Peptides / metabolism
  • Pilot Projects
  • Propanolamines / adverse effects
  • Propanolamines / therapeutic use*
  • Prospective Studies
  • Renal Dialysis / adverse effects*
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Texas
  • Time Factors
  • Treatment Outcome
  • Vascular Stiffness / drug effects
  • Vasodilation / drug effects
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use*

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antigens, CD34
  • Antihypertensive Agents
  • Biomarkers
  • Carbazoles
  • Endothelin-1
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Propanolamines
  • Vasodilator Agents
  • Carvedilol
  • N,N-dimethylarginine
  • Arginine
  • Aldehyde Dehydrogenase

Associated data

  • ClinicalTrials.gov/NCT00827775