title: Effect of low versus high dialysate sodium concentration on blood pressure and endothelial-derived vasoregulators during hemodialysis: a randomized crossover study.
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.
  
  
  METHODS
  3-week, 2-arm, randomized, crossover study.
  
  
  METHODS
  16 patients with intradialytic hypertension.
  
  
  METHODS
  Low (5 mEq/L below serum sodium) versus high (5 mEq/L above serum sodium) dialysate sodium concentration.
  
  
  RESULTS
  Endothelin 1, nitrite (NO2(-)), and BP.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Jula K
authors.initials: JK
authors.lastname: Inrig
authors.affiliation: School of Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Christopher
authors.initials: C
authors.lastname: Molina
authors.affiliation: School of Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Kristin
authors.initials: K
authors.lastname: D'Silva
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Catherine
authors.initials: C
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Peter
authors.initials: P
authors.lastname: Van Buren
authors.affiliation: Department of Internal Medicine, Duke University, Durham, NC.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Allen
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Robert
authors.initials: R
authors.lastname: Toto
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D015314:Dialysis Solutions / Q000008:administration & dosage* / Q000009:adverse effects; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009573:Nitrites / Q000097:blood; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects; D016037:Single-Blind Method; D012964:Sodium / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D015314:Dialysis Solutions; D019332:Endothelin-1; D009573:Nitrites; D012964:Sodium
keywords: Intradialytic hypertension; Mechanisms and Treatment of Intradialytic Hypertension–Sodium (MATCH-NA) Study; blood pressure (BP); dialysate sodium concentration; end-stage renal disease (ESRD); endothelin 1; endothelium; hemodialysis; nitric oxide; nitrite; serum sodium concentration; sodium gradient; vasoregulation