Icodextrin

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.

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.

Small and large animal models, and humans (N = 10) with kidney failure.

30% icodextrin and 10% dextrose IP solution.

We evaluated ultrafiltration (UF), sodium removal, and peritoneal health in animals. We evaluated safety, tolerability, and efficacy in humans.

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.

The long-term safety with chronic therapy and the efficacy in patients without kidney failure were not established and require future studies.

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.

NCT05780086.

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.

The efficacy of icodextrin versus glucose patients undergoing peritoneal dialysis remains unclear. The study was designed to compare the effects of once-daily long-dwell icodextrin versus glucose on markers of hypervolemia and survival among patients with kidney failure undergoing an unplanned initiation of automated peritoneal dialysis.

This was a randomized, non-blinded, and prospective controlled study. Prevalent and stable patients undergoing automated peritoneal dialysis with a recent peritoneal equilibration test showing a dialysate/plasma creatinine of >0.50 were randomized to receive either 7.5% icodextrin or 2.5% glucose solution. Patients were evaluated at baseline (one month after the start of peritoneal dialysis), 3 months, and 6 months after inclusion. The peritoneal dialysis solution was used for at least 3 months, with a follow-up period of 24 months.

Thirty patients were enrolled. There were no baseline differences between the groups. During the study period, patients in the Icodextrin Group showed improvements in the phase angle and ultrafiltration, whereas there were no changes in the Glucose Group. Additionally, extracellular water was significantly lower in the Icodextrin Group at the end of the study than at baseline. No statistical differences between the two groups were observed in urine volume, ultrafiltration, extracellular water, phase angle, renal creatinine clearance, use of diuretics and antihypertensives, or blood pressure. During the 24-month follow-up, the number of events related to overall mortality was seven (Icodextrin Group, n=4; Glucose Group, n=3), with no difference between the groups for this outcome or technique survival.

Icodextrin significantly improved ultrafiltration, extracellular water, and phase angle at the end of the study compared to baseline in patients on the urgent start of automated peritoneal dialysis.

(www.ctri.nic.in) under the number RBR-97z4wh6.