Probing the Mechanisms of Intradialytic Hypertension

Abstract

SummaryBackground 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 functionassessed 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.

Predialysis Systolic BP Variability and Outcomes in Hemodialysis Patients

“…Endothelial cell dysfunction and sympathetic hyperactivity may contribute to higher home, predialysis, and intradialytic BPV, and they may potentially be therapeutic targets with therapies, such as carvedilol or renal denervation. [26][27][28] Our findings have several implications for clinical practice and research. It is important for clinicians to recognize BPV in their dialysis patients as a risk factor for adverse CVevents.…”

Intradialysis Hypertension in End-Stage Renal Disease Patients

“…For example, carvedilol, a β-blocker with vasodilating properties, was shown to improve endothelial dysfunction in vivo 50 and block endothelin-1 release in vitro. 51 In an uncontrolled study, 4 in 25 patients with intradialytic hypertension, carvedilol treatment was associated with an improvement in endothelium-dependent flow-mediated vasodilatation, 4 which was accompanied by reduced occurrence of intradialytic hypertensive episodes during follow-up and with a significant fall (7 mm Hg) in 44-hour ambulatory SBP. 4 Therefore, antihypertensive agents exerting beneficial actions on endothelium, such vasodilating β-blockers, may be of benefit for patients with intradialytic hypertension.…”

“…2,3 The BP rise during dialysis has a complex mechanistic background and is multifactorial in nature. 2,4 Herein, we provide a systematic review of the epidemiology and pathogenesis of intradialytic hypertension and key recommendations for the management of this neglected dialysis-related complication. The search strategy and selection criteria used for this review are reported in Table S1 in the online-only Data Supplement and Figure S1.…”

Assessment and Management of Hypertension in Patients on Dialysis

“…However, the phenomenon of intradialytic hypertension is complex and incompletely understood; pilot studies suggest that endothelial dysfunction may be operative in its pathogenesis. 78 Home BP measurement is a practical way to measure and manage hypertension among HD patients. The targets of therapy using home BP monitoring will need to be defined in future trials.…”