Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in the STZ-induced diabetic rat model with partial nephrectomy

Nephrol Dial Transplant. 2010 May;25(5):1479-88. doi: 10.1093/ndt/gfp479. Epub 2009 Sep 16.

Abstract

Background: Application of icodextrin-based peritoneal dialysis fluid (PDF) provides a potential benefit in patients with diabetes and end-stage renal failure treated with continuous ambulatory peritoneal dialysis (CAPD) because of better ultrafiltration capacity and avoidance of direct glucose exposure. We examined the effect of glucose and icodextrin-based PDF on histological alterations of peritoneal membranes.

Methods: Thirty-two male Wistar rats were divided into four groups: control Wistar rats with non-treated (n = 8), streptozotocin (STZ)-induced diabetic rats with 5/6 kidney ablation (n = 8), STZ-induced diabetic rats with 5/6 kidney ablation injected with a standard lactate-buffered 4.25% glucose-based PDF (Dianeal; n = 8) and STZ-induced diabetic rats with 5/6 kidney ablation injected with 7.5% icodextrin-based PDF (Extraneal; n = 8). Intraperitoneal injection was performed once daily with an instillation volume of 20 ml per injection during 8 weeks.

Results: Chronic high-glucose-based PDF exposure resulted in increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression, accumulation of advanced glycation end-products (AGEs), and up-regulation of the receptor for AGE (RAGE), which were ameliorated in the icodextrin-based PDF group. The peritoneal damages, such as neoangiogenesis and submesothelial fibrosis, were significantly reduced in icodextrin-based PDF compared to high-glucose-based PDF.

Conclusions: Long-term in vivo exposure to high glucose-based PDF promotes the fibrosing process of peritoneal membranes. Icodextrin-based PDF may be helpful in slowing the PDF-induced deterioration of peritoneal function and prolonging the use of peritoneal dialysis in patients with diabetes.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / therapy*
  • Fibroblast Growth Factor 2 / analysis
  • Fibrosis
  • Glucans / pharmacology*
  • Glucose / pharmacology*
  • Glycation End Products, Advanced / analysis
  • Hemodialysis Solutions / pharmacology*
  • Icodextrin
  • Immunohistochemistry
  • Male
  • Nephrectomy
  • Peritoneum / drug effects*
  • Peritoneum / pathology
  • Rats
  • Rats, Wistar
  • Streptozocin
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • Glucans
  • Glycation End Products, Advanced
  • Hemodialysis Solutions
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Icodextrin
  • Streptozocin
  • Glucose