Mechanisms of Intradialytic Hypertension

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Title: Mechanisms of Intradialytic Hypertension
Author: Kim, Bohyun Catherine
Abstract: Intradialytic Hypertension and Its Association with Endothelial Cell Dysfunction Background : 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 greater than or equal to 10 mmHg greater than or equal to 4 /6 consecutive HD sessions ) . The primary outcome was peripheral blood endothelial progenitor cells (EPCs ) assessed by aldehyde dehydrogenase activity (ALDHbr ) 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 ALDHbr cells and decreased CD34+CD133+ cells (ALDHbr , 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 . Probing the Mechanisms of Intradialytic Hypertension : a Pilot Study Targeting Endothelial Cell Dysfunction Background : 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 in vitro to block endothelin -1 release . Among patients with intradialytic hypertension , we hypothesized that carvedilol would improve endothelial cell function and reduce the occurrence of intradialytic hypertension . Design , settings , participants & measurements : We performed a prospective 12 -week pilot study of carvedilol titrated to 50 mg twice daily among 25 hemodialysis participants with intradialytic hypertension . Each patient served as their own control . Changes in endothelial cell function (assessed by flow -mediated vasodilation , endothelial progenitor cells (EPCs by aldehyde dehydrogenase activity and CD34+CD133+ ) , asymmetric dimethylarginine (ADMA ) and endothelin -1 ) and blood pressure (BP ) from baseline to study -end were analyzed by paired tests . Results : Flow -mediated vasodilation was significantly improved with carvedilol (from 1 .03 % to 1 .40 % , p=0 .02 ) . There was no significant change in EPCs , endothelin -1 or ADMA . At baseline , participants exhibited a significant increase in endothelin -1 pre to postdialysis that resolved by study -end . While pre -hemodialysis systolic BP was unchanged (144 to 146 mmHg , p=0 .5 ) , post -hemodialysis systolic BP , 44 -hour ambulatory systolic BP , and the frequency of intradialytic hypertension 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 ) . Conclusions : Among hemodialysis participants with intradialytic hypertension , targeting endothelial cell dysfunction with carvedilol was associated with modest improvements in endothelial cell function , improved intra and interdialytic BP , and reduced frequency of intradialytic hypertension . Randomized controlled trials are required to confirm these findings . The Role of Dialysate Exposure in Intradialytic Hypertension Background : Intradialytic hypertension is associated with endothelial dysfunction , but the cause of vascular impairment is unknown . Exposure to high concentration sodium has been shown in vitro to promote endothelial stiffness and imbalances in markers of vascular function . We hypothesized that , among patients with intradialytic hypertension , exposure to dialysate sodium would lead to increases in endothelin -1 , decreases in nitric oxide , and an intradialytic increase in systolic blood pressure . Design , settings , participants & measurements : We performed a 6 -week crossover study of 10 hemodialysis patients with intradialytic hypertension . Changes in blood pressure , endothelin -1 , and nitric oxide levels were measured during three different , midweek dialysis treatments consisting of : 1 ) regular hemodialysis with standard dialysate sodium (140 mEq /L ) ; 2 ) ultrafiltration only without dialysate exposure ; and 3 ) hemodialysis (Na 140 mEq /L ) without ultrafiltration . These changes were analyzed using mixed model analyses . Results : Serum sodium levels rose with dialysate exposure during regular HD and HD without UF sessions (+1 .6 and +3 mEq /L , respectively ) , and fell during UF only session ( -0 .9 mEq /L ) . Endothelin -1 level also rose with dialysate exposure during regular HD and HD without UF (+0 .15 and +0 .25pg /mL , respectively ) , but fell during UF only session ( -0 .02 pg /mL ) . Plasma nitrite levels fell with all treatment types , most significantly with regular HD ( -123 .25 nM ) , then HD without UF ( -52 .77 nM ) , with lowest decrease seen during UF only session without dialysate exposure ( -48 .48 nM ) . Systolic BP rose during all treatments , most significantly with HD without UF (13 .3 % ) , followed by regular dialysis (6 .9 % ) , and UF only (5 .7 % ) . Conclusions : Among hemodialysis patients prone to intradialytic hypertension , there was an association between dialysate exposure and increases in endothelin -1 , decreases in nitric oxide , and increases in systolic blood pressure during dialysis . We propose that high dialysate to plasma sodium gradient may contribute to intradialytic hypertension . [Keywords : hemodialysis ; intradialytic hypertension ; Carvedilol ; endothelial cell dysfunction ; endothelial progenitor cells]
URI: http : / /hdl .handle .net /2152 .5 /1118
Date: 2012-08-15

Citation

Mechanisms of Intradialytic Hypertension. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /1118 .

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