Intradialytic hypertension and its association with endothelial cell dysfunction.
ABSTRACT 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.
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 ≥10 mmHg ≥4/6 consecutive HD sessions). The primary outcome was peripheral blood endothelial progenitor cells (EPCs) assessed by aldehyde dehydrogenase activity (ALDH(br)) 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.
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 ALDH(br) cells and decreased CD34(+)CD133(+) cells (ALDH(br), 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%).
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.
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ABSTRACT: It is not clear to what extent changes in blood pressure (BP) during hemodialysis affect or predict survival. Studying comparative outcomes of BP changes during hemodialysis can have major clinical implications including the impact on management strategies in hemodialysis patients. Here we undertook a retrospective cohort study of 113,255 hemodialysis patients over a 5-year period to evaluate an association between change in BP during hemodialysis and mortality. The change in BP was defined as post-hemodialysis minus pre-hemodialysis BP, and mean of BP change values during the hemodialysis session was used as a mortality predictor. The patients' average age was 61 years old and consisted of 45% women, 32% African-Americans and 58% diabetics. Over a median follow-up of 2.2 years, a total of 53,461 (47.2%) all-cause and 21,548 (25.7%) cardiovascular deaths occurred. In a fully adjusted Cox regression model with restricted cubic splines, there was a U-shaped association between change in systolic BP and all-cause mortality. Post-dialytic drops in systolic BP between -30 and 0 mm Hg were associated with greater survival, but large decreases of systolic BP (more than -30 mm Hg) and any increase in systolic BP (over 0 mm Hg) were related to increased mortality. Peak survival was found at a change in systolic BP of -14 mm Hg. The U-shaped association was also found for cardiovascular mortality. Thus, modest declines in BP after hemodialysis are associated with the greatest survival, whereas any rise or large decline in BP is associated with worsened survival.Kidney International advance online publication, 19 June 2013; doi:10.1038/ki.2013.237.Kidney International 06/2013; · 8.52 Impact Factor
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ABSTRACT: The field of uremic toxicity comprises the study of a large number of different substances, classified in relation to various characteristics, for example protein-binding, dimensions, etc. The endogenous compounds of gaseous nature have lately received much attention from the scientific community, because of their increasingly recognized importance in health and disease. Among these substances, some are uremic toxins per se, others are related to uremic toxins, or can become toxic under some circumstances. We divided them into two broad categories: organic and inorganic compounds. Among the organic compounds, we find phenols, indols, 2-methoxyresorcinol, p-hydroxy hippuric acid, and phenyl acetic acid, trimethylamine and dimethylamine; among the inorganic solutes, ammonia, nitric oxide, carbon monoxide, and hydrogen sulfide. In this chapter, these substances are described in relation to the elements that they affect or by which they are affected in uremia, which are the blood, breath, stools and the gastrointestinal tract, and this in general and during the dialysis procedure.Seminars in Nephrology 01/2014; · 2.83 Impact Factor
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ABSTRACT: Park et al. performed a retrospective analysis of a large hemodialysis cohort to describe the relationship between pre- to postdialysis changes in BP and mortality. Their study demonstrated adverse outcomes associated both with large decreases and with any increase in blood pressure pre- to postdialysis. Although limitations exist in this analysis, which lacked intradialytic blood pressure measurements, the results support the ongoing concern about the potential adverse hemodynamic stress associated with conventional three-times-weekly hemodialysis.Kidney International 10/2013; 84(4):641-644. · 8.52 Impact Factor