Kidney Medicine (Jan 2025)
Development of a Novel Intraperitoneal Icodextrin/Dextrose Solution for Enhanced Sodium Removal
Abstract
Rationale & Objective: Peritoneal dialysis (PD) solutions provide both clearance of uremic toxins and sodium and water. An intraperitoneal (IP) solution of icodextrin and glucose designed without the requirement for uremic toxin clearance could provide substantially greater sodium and water removal than PD solutions. Study Design: We examined varying concentrations of icodextrin and dextrose IP solutions in rats. We evaluated a 30% icodextrin and 10% dextrose IP solution in animals and humans. Participants: Small and large animal models, and humans (N = 10) with kidney failure. Exposure: 30% icodextrin and 10% dextrose IP solution. Outcomes: We evaluated ultrafiltration (UF), sodium removal, and peritoneal health in animals. We evaluated safety, tolerability, and efficacy in humans. Results: In rats, increasing concentrations of icodextrin and dextrose IP solutions, up to 30% icodextrin and 10% dextrose, produced progressively greater UF (P < 0.001). In sheep treated with 30% icodextrin and 10% dextrose, the mean UF was ∼3.5-fold greater (1.77 ± 0.22 L vs 0.47 ± 0.34 L; P = 0.005) and the mean sodium removal was ∼4-fold greater (7.07 ± 0.72 g vs 1.78 ± 1.27 g; P = 0.003) compared with commercially available 7.5% icodextrin PD solution. Long-term exposure of mice (30 days) and sheep (30-45 days) to a 30% icodextrin and 10% dextrose IP solution resulted in no significant structural tissue changes compared with the control 4.25% commercially available PD solution. In humans, a 24-hour dwell of a 30% icodextrin and 10% dextrose IP solution resulted in median net UF of 2,498 mL (IQR, 2,249-2,768), and median sodium removal of 387 mmol (IQR, 372-434 mmol). No serious adverse events occurred. Limitations: The long-term safety with chronic therapy and the efficacy in patients without kidney failure were not established and require future studies. Conclusions: A 30% icodextrin and 10% dextrose IP solution provides more efficient UF and sodium removal than traditional PD solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure. Clinical Trial Registration: NCT05780086. Summary: We aimed to design a novel intraperitoneal solution designed for optimal sodium and water removal. A sodium-free 30% icodextrin and 10% dextrose intraperitoneal solution was evaluated in animal models and humans to determine the safety and efficacy. A 30% icodextrin and 10% dextrose solution provides more efficient sodium and water removal than traditional peritoneal dialysis solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure. Plain-Language Summary: We aimed to design a novel intraperitoneal solution designed for optimal sodium and water removal. A sodium-free 30% icodextrin and 10% dextrose intraperitoneal solution was evaluated in animal models and humans to determine the safety and efficacy. A 30% icodextrin and 10% dextrose solution provides more efficient sodium and water removal than traditional peritoneal dialysis solutions. The promising inhuman safety and efficacy results warrant future investigation as a sodium removal therapy in patients with edematous disorders such as heart failure.
