title: Hyperbranched polyglycerol is superior to glucose for long-term preservation of peritoneal membrane in a rat model of chronic peritoneal dialysis.
abstract: Replacing 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.
  
  
  
  Adult 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.
  
  
  
  Here, 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.
  
  
  
  The 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.
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. caigan@mail.ubc.ca.|Jack Bell Research Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada. caigan@mail.ubc.ca.
authors.forename: Caigan
authors.initials: C
authors.lastname: Du
authors.affiliation: Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.|London Health Sciences Centre, London, ON, Canada.
authors.forename: Asher A
authors.initials: AA
authors.lastname: Mendelson
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Qiunong
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Ghida
authors.initials: G
authors.lastname: Dairi
authors.affiliation: Department of Pathology and Laboratory Medicine, Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Irina
authors.initials: I
authors.lastname: Chafeeva
authors.affiliation: Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Gerald
authors.initials: G
authors.lastname: da Roza
authors.affiliation: Department of Pathology and Laboratory Medicine, Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.|Department of Chemistry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jayachandran N
authors.initials: JN
authors.lastname: Kizhakkedathu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D015314:Dialysis Solutions / Q000494:pharmacology*; D004195:Disease Models, Animal; D005947:Glucose / Q000494:pharmacology*; D005990:Glycerol / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000187:drug effects* / Q000473:pathology; D011108:Polymers / Q000494:pharmacology*; D011309:Preservation, Biological; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000199:Actins; D015314:Dialysis Solutions; D005947:Glucose; D005990:Glycerol; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A; C498862:Acta2 protein, rat; C043941:polyglycerol
keywords: Biocompatibility; Hyperbranched polyglycerol; Long-term PD; PD solution; Peritoneal membrane