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: Background and Objectives: Erythropoiesis-stimulating agents (ESAs) might moderate circu-lating CD34-positive hematopoietic stem (CD34 +) cells. We assessed associations between ESA therapy and CD34 + cells and their impact on cardiovascular disease (CVD) events in patients on prevalent hemodialysis (HD). Design, Setting, Participants and Measurements: We analyzed 95 patients on prevalent HD who received the ESAs epoetin-(n = 22), darbepoetin-(n = 60), or neither (control; no ESA, n = 13). Baseline values for CD34 + cells, high-sensitivity C-reactive protein, interleukin-6, vascular endothelial growth factor, inter-cellular adhesion molecule-1, and carotid intima-media thickness were determined. The numbers of CD34 + /erythropoietin receptor (EPOR) + cells were determined in 35 and 8 patients in the darbepoetin-and control groups, respectively. CD34 + cells were counted after 6 and 12 months of darbepoetin-treat-ment (n = 35). All patients were followed up for a mean of 28 months. Results: Hemoglobin levels were lower, carotid intima-media thickness was more pronounced, and the ESA dose was higher in patients with a low, than with a high, CD34 + cell count. The ratio of CD34 + /EPOR + to CD34 + cells positively correlated with the darbepoetin-dose. A low, but not a high, dose of darbepoetin-for 6 and 12 months was associated with more CD34 + cells. Although high-dose darbepoetin-therapy was an independent predictor of composite CVD events, this associa-tion disappeared when adjusted for the CD34 + cell count with other confounders. Conclusions: High-dose ESA therapy is associated with a low CD34 + cell count and comprises a risk factor for CVD events in patients on prevalent HD.
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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 03/2014; DOI:10.1016/j.semnephrol.2014.02.006 · 2.94 Impact Factor
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ABSTRACT: Intradialytic hypertension affects ∼15% of hemodialysis patients and is associated with increased morbidity and mortality. While intradialytic hypertension is associated with increases in endothelin 1 relative to nitric oxide (NO), the cause of these imbalances is unknown. In vitro evidence suggests that altering plasma sodium levels could affect endothelial-derived vasoregulators and blood pressure (BP). Thus, we hypothesized that compared to high dialysate sodium, low dialysate sodium concentration would lower endothelin 1 levels, increase NO release, and reduce BP. 3-week, 2-arm, randomized, crossover study. 16 patients with intradialytic hypertension. Low (5 mEq/L below serum sodium) versus high (5 mEq/L above serum sodium) dialysate sodium concentration. Endothelin 1, nitrite (NO2(-)), and BP. Mixed linear regression was used to compare the effect of dialysate sodium (low vs high) and randomization arm (low-then-high vs high-then-low) on intradialytic changes in endothelin 1, NO2(-), and BP values. The average systolic BP throughout all hemodialysis treatments in a given week was lower with low dialysate sodium concentrations compared with treatments with high dialysate sodium concentrations (parameter estimate, -9.9 [95% CI, -13.3 to -6.4] mm Hg; P < 0.001). The average change in systolic BP during hemodialysis also was significantly lower with low vs high dialysate sodium concentrations (parameter estimate, -6.1 [95% CI, -9.0 to -3.2] mm Hg; P < 0.001). There were no significant differences in intradialytic levels of endothelin 1 or NO2(-) with low vs high dialysate sodium concentrations. Carryover effects limited the power to detect significant changes in endothelial-derived vasoregulators, and future studies will require parallel trial designs. Low dialysate sodium concentrations significantly decreased systolic BP and ameliorated intradialytic hypertension. Longer studies are needed to determine the long-term effects of low dialysate sodium concentrations on BP and clinical outcomes. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.American Journal of Kidney Diseases 12/2014; 65(3). DOI:10.1053/j.ajkd.2014.10.021 · 5.76 Impact Factor