Hemodialysis.com

Hemodialysis.com: What are the main findings of the study?

Intradialytic hypertension may be caused by an impaired endothelial cell response to hemodialysis and we hypothesized that carvedilol (which has been shown in vivo and in vitro to block endothelin-1 release) would improve endothelial cell function and reduce the occurrence of intradialytic hypertension. 

To test this hypothesis, we performed a prospective 12-week pilot study of carvedilol titrated to 50 mg twice daily among 25 hemodialysis participants with intradialytic hypertension and measured changes in endothelial cell function and BP.  

We found significant improvements in endothelial cell function with carvedilol as measured by improved flow-mediated vasodilation (from 1.03% to 1.40%, p=0.02). 

While we found no significant change in endothelial progenitor cells (EPCs), participants were found to have a significant increase in endothelin-1 pre to postdialysis at baseline that resolved by study-end. 

While pre-hemodialysis systolic BP was unchanged during the study (144 to 146 mmHg, p=0.5), post-hemodialysis systolic BP, 44-hour ambulatory systolic BP, and the frequency of intradialytic hypertension significantly decreased with carvedilol (159 to 142 mmHg, p<0.0001; 155 to 148 mmHg, p=0.05; 77% (4.6/6) to 28% (1.7/6), p<0.0001, respectively).

Hemodialysis.com: Were any of the findings unexpected?

By study end, 15/25 patients had complete resolution of intradialytic hypertension while 10 continued to have an increase in BP during hemodialysis. 

Among those with resolution of intradialytic hypertension, there were significant improvements in most markers of EC function (flow-mediated vasodilation, EPCs, ADMA, and endothelin-1), while those who failed to resolve their intradialytic hypertension had either no improvement or worsening markers of EC function.

Hemodialysis.com: What should clinicians and patients take away from this study?

Among patients with intradialytic hypertension, carvedilol was associated with improvements in endothelial cell function, reduced interdialytic BP, and a reduced frequency of intradialytic hypertension. 

This study supports the hypothesis that targeting EC dysfunction may represent a therapeutic approach to manage patients with intradialytic hypertension, however this requires testing in randomized controlled trials.

Hemodialysis.com:What recommendations do you have for future studies as a result of your study?

Future studies are aimed at understanding how dialysis may impair endothelial cell function. 

Furthermore, a randomized controlled trial of carvedilol among patients with intradialytic hypertension is warranted.