title: 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.
authors.affiliation: Medical Products (Renal), Baxter Healthcare Corporation, Deerfield, Illinois, USA ken_leypoldt@baxter.com.
authors.forename: John K
authors.initials: JK
authors.lastname: Leypoldt
authors.affiliation: Medical Products (Renal), Baxter Healthcare Corporation, Deerfield, Illinois, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Hoff
authors.affiliation: Medical Products (Renal), Baxter Healthcare Corporation, Deerfield, Illinois, USA.
authors.forename: Alp
authors.initials: A
authors.lastname: Akonur
authors.affiliation: Medical Products (Renal), Baxter Healthcare Corporation, Deerfield, Illinois, USA.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Holmes
mesh_terms: D000818:Animals; D003198:Computer Simulation; D015314:Dialysis Solutions / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005260:Female; D005936:Glucans / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D000077607:Icodextrin; D008962:Models, Theoretical; D008970:Molecular Weight; D009995:Osmosis / Q000187:drug effects; D010530:Peritoneal Dialysis / Q000009:adverse effects / Q000379:methods*; D011108:Polymers / Q000494:pharmacology; D011817:Rabbits; D011897:Random Allocation; D051437:Renal Insufficiency / Q000628:therapy*; D012680:Sensitivity and Specificity; D014462:Ultrafiltration / Q000379:methods
chemical_list: D015314:Dialysis Solutions; D005936:Glucans; D011108:Polymers; D000077607:Icodextrin; D005947:Glucose
keywords: Carbohydrate absorption; glucose polymer; molecular weight; polydispersity; rabbits; ultrafiltration