First-in-Human Experience With Peritoneal Direct Sodium Removal Using a Zero-Sodium Solution: A New Candidate Therapy...

Area of Science:

• Nephrology
• Cardiology
• Biomedical Engineering

Background:

• Loop diuretics are common for heart failure (HF) but have toxicities and can lose effectiveness.
• Alternative strategies are needed to maintain euvolemia in HF patients.
• Direct sodium removal (DSR) via the peritoneal membrane offers a nonrenal sodium extraction method with a sodium-free osmotic solution.

Purpose of the Study:

• To describe the preclinical development of DSR.
• To establish a first-in-human proof of concept for DSR.
• To evaluate DSR's safety, efficacy, and scalability in managing fluid overload.

Main Methods:

• Preclinical studies in pigs investigated DSR using 10% dextrose solution, assessing dwell time, safety, and scalability in experimental heart failure.
• A human proof-of-concept study randomized end-stage renal disease patients on peritoneal dialysis (PD) to DSR or standard PD.
• Primary endpoint was tolerability; secondary endpoint was sodium removal difference.

Main Results:

• Porcine studies showed DSR removed 4.1g sodium in 2 hours with stable electrolytes and minimal off-target solute removal.
• Increased DSR volume enhanced sodium removal and decreased plasma volume in pigs.
• Human study demonstrated DSR was well-tolerated, removed significantly more sodium (4.5g vs 1.0g) than standard PD, with stable electrolytes and negligible off-target solute removal.

Conclusions:

• Direct sodium removal (DSR) is well-tolerated in animals and humans.
• DSR achieved substantially greater sodium removal compared to standard peritoneal dialysis.
• Further research is warranted to evaluate DSR for preventing and treating hypervolemia in heart failure.