Abstract: TH-PO1229
Effects of Sodium-Free Chloride Supplementation on Cardiorenal Function in Chronic Heart Failure
Session Information
- Late-Breaking Research Posters
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Cox, Zachary L., Lipscomb University, Nashville, Tennessee, United States
- Rao, Veena, Yale University, New Haven, Connecticut, United States
- Ivey-Miranda, Juan B., Yale University, New Haven, Connecticut, United States
- Moreno Villagómez, Julieta, Yale University, New Haven, Connecticut, United States
- Ramos-Mastache, Daniela, Yale University, New Haven, Connecticut, United States
- Testani, Jeffrey M., Yale University, New Haven, Connecticut, United States
Background
Volume overload in heart failure (HF) is managed with loop diuretics and salt restriction. This strategy is often ineffective and can worsen sodium avidity and neurohormonal activation. Increased salt intake improves neurohormones and sodium avidity, but often at the expense of worsened volume status. While sodium is the key driver of congestion, renal salt sensing mechanisms largely rely on chloride. We aimed to evaluate if sodium-free chloride supplementation could improve diuretic response, sodium avidity, and intravascular volume.
Methods
Patients with stable, euvolemic HF and serum chloride < 102mEq/L requiring >40mg of oral furosemide/day were randomized in a double-blind, placebo-controlled, crossover trial of 5 days of lysine chloride (165mmol/day in 3 divided doses) or matching placebo. The primary outcome was the change in total blood volume (determined with I-131 radiolabeled albumin). Secondary outcomes were change in natriuresis to IV bumetanide and the ability to renally excrete a saline load.
Results
A total of 20 patients (mean age 55 years, 70% male) were enrolled with median furosemide dose of 80mg/day (IQR 40, 200). Serum chloride increased from 98±3 mEq/L at baseline to 104±4 mEq/L with lysine chloride. Blood volume (-289±390 mL vs 34±548 mL; P=0.03) and plasma volume (-152±294 mL vs 50±382 mL; P=0.02) improved significantly more with lysine chloride. 6-hour natriuresis following IV bumetanide improved with lysine chloride (90±39 mmoLNa vs 63±36 mmoL Na; P<0.001) versus placebo. 6-hour natriuresis following 1L normal saline also was superior with lysine chloride (160±59 mmoL vs 115±53 mmoL; P=0.006) versus placebo. Despite the reduction in intravascular volume, changes in serum creatinine (P=0.69) and cystatin C (P=0.78) were not different between groups.
Conclusion
Sodium-free chloride supplementation improved total blood volume, diuretic-induced natriuresis, and ability to excrete a sodium load without worsening kidney function. These proof-of-concept results indicate chloride supplementation may modulate renal salt sensing and improve volume status and sodium avidity in human HF.