Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in the STZ-induced diabetic rat model with partial nephrectomy.
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.
Nakao
Ai
A
Department of Medicine and Clinical Science and 2Center for Chronic Kidney Disease and Peritoneal Dialysis, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. nakao_kazu@ybb.ne.jp
Nakao
Kazushi
K
Takatori
Yuji
Y
Kojo
Syoichirou
S
Inoue
Junko
J
Akagi
Shigeru
S
Sugiyama
Hitoshi
H
Wada
Jun
J
Makino
Hirofumi
H
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000628:therapy*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D005355:Fibrosis; D005936:Glucans / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000032:analysis; D015312:Hemodialysis Solutions / Q000494:pharmacology*; D000077607:Icodextrin; D007150:Immunohistochemistry; D008297:Male; D009392:Nephrectomy; D010537:Peritoneum / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D005936:Glucans; D017127:Glycation End Products, Advanced; D015312:Hemodialysis Solutions; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000077607:Icodextrin; D013311:Streptozocin; D005947:Glucose