Low-Polydispersity Glucose Polymers as Osmotic Agents for Peritoneal Dialysis

Abstract

♦

Background: Peritoneal dialysis (PD) solutions containing icodextrin as the osmotic agent have advantages during long dwells. The glucose polymers that constitute icodextrin are a heterogeneous mix of molecules with a polydispersity [ratio of weight-average to number-average molecular weight (Mw/Mn)] of approximately 2.6. The present study evaluates whether modifications in the polydispersity and concentration of glucose polymers can improve ultrafiltration (UF) without an associated increase in carbohydrate absorption (CA). ♦

Methods: Computer simulations using a three-pore model of peritoneal transport during a long dwell in PD patients predict that, in general, compared with 7.5% icodextrin, glucose polymers with a Mw greater than or equal to 7.5 kDa, a polydispersity less than 2.6, and concentrations greater than 7% could achieve higher UF without higher CA. Based on the simulations, we hypothesized that, compared with 7.5% icodextrin, glucose polymers with a Mw of 18 - 19 kDa and a polydispersity of 2.0 at 11% concentration could achieve higher UF without a higher CA. We tested this hypothesis in experimental studies using 8-hour dwells in New Zealand White rabbits. In those studies, UF was measured by complete fluid collection, and CA was measured by subtracting the total carbohydrate in the collected fluid from the carbohydrate initially infused. ♦

Results: The UF was higher with 11% 19 kDa glucose polymer than with 7.5% icodextrin (mean ± standard deviation: 89 ± 31 mL vs 49 ± 15 mL; p = 0.004) without higher CA (5.2 ± 0.9 g vs 5.0 ± 0.9 g, p = 0.7). Similar results were seen with the 11% 18 kDa glucose polymer, which, compared with 7.5% icodextrin, resulted in higher UF (mean ± standard deviation: 96 ± 18 mL vs 66 ± 17 mL; p < 0.001) without higher CA (4.8 ± 0.7 g vs 5.2 ± 0.6 g, p = 0.2). ♦

Conclusions: The findings demonstrate that, compared with 7.5% icodextrin solution, long-dwell PD solutions containing 11% glucose polymers with a Mw of 18-19 kDa and a polydispersity of 2.0 can provide higher UF without higher CA.

Keywords: Carbohydrate absorption; glucose polymer; molecular weight; polydispersity; rabbits; ultrafiltration.

Figure 1 —

Theoretical predictions from a three-pore model of peritoneal transport: net ultrafiltration and carbohydrate absorbed with different glucose polymers as the osmotic agent for a high-transport patient. The large circle indicates the calculated result for 7.5% icodextrin; the solid and dashed lines indicate the calculated results for glucose polymers with weight-average molecular weights of 6 kDa and 19 kDa respectively. The calculated results for the glucose polymers also reflect various polydispersities—1.6 (diamonds), 2.0 (squares), and 2.4 (triangles)—and various percentage concentrations.

Figure 2 —

Molecular weight distribution of the 19K glucose polymer (black bars) and icodextrin (white bars), determined using methods described by García–López and Lindholm (–13). Mean values from 4 separate determinations at a total polymer concentration of 7.5 g/dL are shown.

Figure 3 —

Net ultrafiltration and carbohydrate absorbed during study 1: the 19K glucose polymer at a concentration of 11% (white bars) and icodextrin at a concentration of 7.5% (black bars).

Figure 4 —

Net ultrafiltration and carbohydrate absorbed during study 2: the 18K glucose polymer at a concentration of 11% (white bars) and icodextrin at a concentration of 7.5% (black bars).

Figure 5 —

Net ultrafiltration and carbohydrate absorbed during the control study: the 19K glucose polymer at a concentration of 11% (white bars) and icodextrin at a concentration of 11% (black bars).