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

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.

Figures

Figure 1.

Study flow chart of participants with intradialytic hypertension in the Mechanisms and Treatment of Intradialytic Hypertension Study. EPC, endothelial progenitor cells; ABP, ambulatory BP; SBP, systolic BP.

Figure 2.

Change in individual brachial artery flow-mediated vasodilation from baseline to study. Mean flow-mediated vasodilation at baseline was 1.03, which improved to 1.40 by study end (P=0.02). Each marker and line represent an individual participant in the study.

Figure 3.

Changes in systolic BP during the Mechanisms and Treatment of Intradialytic Hypertension (MATCH) Study. (A) Two-week screening hemodialysis unit systolic BP and subsequent weekly average standardized predialysis and postdialysis systolic BP during the course of the study. (B) Change in individual 2-week average predialysis and postdialysis systolic BP from baseline to study end. Mean predialysis systolic BP was unchanged from baseline (144–146.1 mmHg, P=0.5), whereas mean postdialysis systolic BP was significantly reduced (from 159 to 142.4 mmHg, P<0.001). PreHD SBP, prehemodialysis systolic BP; postHD SBP, posthemodialysis systolic BP.