Cyclosporin A induces peritoneal fibrosis and angiogenesis during chronic peritoneal exposure to a glucose-based, lactate-buffered dialysis solution in the rat.
OBJECTIVE
Cyclosporin A (CsA) stimulates the development of fibrosis. We investigated whether CsA contributes to peritoneal alterations induced by long-term exposure to dialysis solutions.


METHODS
Ten rats received peritoneal infusion of dialysis solution and oral CsA for 8 weeks. Eight received only the dialysis solution (controls). Peritoneal function was assessed at 8 weeks followed by sacrifice. The number of vessels was counted, fibrosis was assessed and hydroxyproline was determined. PCR was performed for vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and transforming growth factor-beta (TGF-beta).


RESULTS
Histology revealed more fibrosis, hydroxyproline and vessels (thick walled) in CsA-exposed animals. Peritoneal transport was not different. The mRNA content of TGF-beta, CTGF and VEGF was higher in CsA.


CONCLUSIONS
CsA combined with exposure to dialysis solutions was associated with increased peritoneal fibrosis and angiogenesis.
van Westrhenen
Roos
R
Department of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Aten
Jan
J
Hajji
Najat
N
de Boer
Onno J
OJ
Kunne
Cindy
C
de Waart
Dirk R
DR
Krediet
Raymond T
RT
D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D005355:Fibrosis / Q000139:chemically induced*; D005947:Glucose / Q000627:therapeutic use; D015312:Hemodialysis Solutions / Q000009:adverse effects* / Q000737:chemistry; D019344:Lactic Acid / Q000627:therapeutic use; D008297:Male; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010532:Peritoneal Diseases / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D015312:Hemodialysis Solutions; D019344:Lactic Acid; D016572:Cyclosporine; D005947:Glucose