Hyperbranched polyglycerol is superior to glucose for long-term preservation of peritoneal membrane in a rat model of chronic peritoneal dialysis

Abstract

BackgroundReplacing glucose with a better biocompatible osmotic agent in peritoneal dialysis (PD) solutions is needed in PD clinic. We previously demonstrated the potential of hyperbranched polyglycerol (HPG) as a replacement for glucose. This study further investigated the long-term effects of chronic exposure to HPG as compared to a glucose-based conventional PD solution on peritoneal membrane (PM) structure and function in rats.MethodsAdult male Wistar rats received once-daily intraperitoneal injection of 10 mL of HPG solution (1 kDa, HPG 6%) compared to Physioneal™ 40 (PYS, glucose 2.27%) or electrolyte solution (Control) for 3 months. The overall health conditions were determined by blood chemistry analysis. The PM function was determined by ultrafiltration, and its injury by histological and transcriptome-based pathway analyses.ResultsHere, we showed that there was no difference in the blood chemistry between rats receiving the HPG and the Control, while PYS increased serum alkaline phosphatase, globulin and creatinine and decreased serum albumin. Unlike PYS, HPG did not significantly attenuate PM function, which was associated with smaller change in both the structure and the angiogenesis of the PM and less cells expressing vascular endothelial growth factor, α-smooth muscle actin and MAC387 (macrophage marker). The pathway analysis revealed that there were more inflammatory signaling pathways functioning in the PM of PYS group than those of HPG or Control, which included the signaling for cytokine production in both macrophages and T cells, interleukin (IL)-6, IL-10, Toll-like receptors, triggering receptor expressed on myeloid cells 1 and high mobility group box 1.ConclusionsThe results from this experimental study indicate the superiority of HPG to glucose in the preservation of the peritoneum function and structure during the long-term PD treatment, suggesting the potential of HPG as a novel osmotic agent for PD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1098-z) contains supplementary material, which is available to authorized users.

Peritoneal and Systemic Responses of Obese TypeIIDiabetic Rats to Chronic Exposure to a Hyperbranched Polyglycerol‐Based Dialysis Solution

“…PYS (Physioneal™ 40 solution, 2.27% glucose w/v) and ICO (Extraneal™, 7.5% icodextrin w/v) were purchased from Baxter Healthcare Co. (Deerfield, IL, USA). HPG (1 kDa) was synthesized by an anionic ring opening multibranching polymerization and characterized following our previous reports . A HPG PD solution (denoted as HPG, 6% HPG, approximately 402 mOsmol/kg, pH 7.4) and electrolyte control (denoted as Control, 251 mOsmol/kg, pH 7.4) solutions were prepared as reported previously .…”

“…Obese diabetic rats received a once‐daily IP injection of 10 mL of the PD solution or Control as previously established in our laboratory . In brief, after anaesthesia with isoflurane, 10 mL of a pre‐warmed PD solution (Control, PYS, ICO or HPG) was slowly injected into the peritoneal cavity at the abdominal midline.…”

“…Low molecular weight hyperbranched polyglycerol (HPG, 0.5–3 kDa) has recently been tested as a novel osmotic agent in the development of a glucose‐sparing PD solution . It has been shown that HPG‐based PD solutions induce similar or improved efficacy of fluid removal and reduce the level of peritoneal membrane (PM) damage compared to conventional glucose‐based dianeal or physioneal (denoted as PYS) PD solutions in rat models of PD . However, the local and systemic effects of chronic exposure to a HPG‐based PD solution under the condition of MetS have not been investigated.…”

Visions in a Crystal Ball: The Future of Peritoneal Dialysis

“…Theoretically, the molecular properties of HPG make it more efficient than glucose in producing ultrafiltration. Promising studies [15, 16] in rodents showed better preservation of UF and fewer toxic effects on the peritoneal membrane. However, studies in humans have not yet been conducted, and there are several questions remaining such as the ramifications of accumulation of HPG over time, or whether HPG molecules are metabolized in plasma and in the peritoneal cavity.…”

“…However, studies in humans have not yet been conducted, and there are several questions remaining such as the ramifications of accumulation of HPG over time, or whether HPG molecules are metabolized in plasma and in the peritoneal cavity. Also, the long-term biocompatibility over years remains unclear, with the longest animal experiment using the solution for 3 months [15]. …”