Effect of Low Versus High Dialysate Sodium Concentration on Blood Pressure and Endothelial-Derived Vasoregulators During Hemodialysis: A Randomized Crossover Study

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. Invitro 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.