Jula K Inrig1, Christopher Molina2, Kristin D'Silva2, Catherine Kim3, Peter Van Buren4, Jason D Allen5, Robert Toto4. 1. Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX; Department of Internal Medicine, Duke University, Durham, NC; Department of Medicine, Quintiles Global Clinical Research Organization, Morrisville, NC. Electronic address: jula.inrig@duke.edu. 2. School of Medicine, University of Texas Southwestern Medical Center, Dallas, TX. 3. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. 4. Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. 5. Department of Internal Medicine, Duke University, Durham, NC.
Abstract
BACKGROUND: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. STUDY DESIGN: 3-week, 2-arm, randomized, crossover study. SETTING & PARTICIPANTS: 16 patients with intradialytic hypertension. INTERVENTION: Low (5 mEq/L below serum sodium) versus high (5 mEq/L above serum sodium) dialysate sodium concentration. OUTCOMES: Endothelin 1, nitrite (NO2(-)), and BP. MEASUREMENTS: 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. RESULTS: 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 BPduring 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. LIMITATIONS: Carryover effects limited the power to detect significant changes in endothelial-derived vasoregulators, and future studies will require parallel trial designs. CONCLUSIONS: 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.
RCT Entities:
BACKGROUND: 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. STUDY DESIGN: 3-week, 2-arm, randomized, crossover study. SETTING & PARTICIPANTS: 16 patients with intradialytic hypertension. INTERVENTION: Low (5 mEq/L below serum sodium) versus high (5 mEq/L above serum sodium) dialysate sodium concentration. OUTCOMES: Endothelin 1, nitrite (NO2(-)), and BP. MEASUREMENTS: 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. RESULTS: 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. LIMITATIONS: Carryover effects limited the power to detect significant changes in endothelial-derived vasoregulators, and future studies will require parallel trial designs. CONCLUSIONS: 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.
Authors: Kristen L Nowak; Michel Chonchol; Anna Jovanovich; Zhiying You; Jeffrey Bates; Capri Foy; Stephen Glasser; Anthony A Killeen; John Kostis; Carlos J Rodriguez; Mark Segal; Debra L Simmons; Addison Taylor; Laura C Lovato; Walter T Ambrosius; Mark A Supiano Journal: Am J Hypertens Date: 2019-06-11 Impact factor: 2.689
Authors: Amith Roy Shamir; Ameet Karembelkar; Jonathan Yabes; Yi Yao; Dana Miskulin; Jennifer Gassman; David Ploth; Lavinia Negrea; Susan Paine; Mahboob Rahman; Raymond Y Kwong; Philip Zager; Manisha Jhamb Journal: Kidney Blood Press Res Date: 2018-05-30 Impact factor: 2.687