A chronic inflammatory infusion model of peritoneal dialysis in rats.
OBJECTIVE
Peritoneal membrane changes are related to daily exposure to non physiologic dialysate and recurrent acute inflammation. We modified a daily infusion and inflammation model and evaluated it for fibrotic and angiogenic features. The feasibility of adenovirus-mediated gene transfer in the model was also assessed.


METHODS
Peritoneal catheters were implanted in rats. Over a period of 4 weeks, the animals received a daily infusion of Dianeal 4.25% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) with an initial three doses of lipopolysaccharide (LPS) or physiologic saline. Peritoneal fluid was assayed for transforming growth factor beta (TGFbeta) and vascular endothelial growth factor (VEGF). Animals were humanely killed at week 5. Net ultrafiltration was then measured, and tissue samples were immunostained for factor VIII. Mesenteric tissue was assayed for hydroxyproline content. Adenovirus-mediated gene transfer of beta-galactosidase was assayed by intraperitoneal administration of the virus, 4 days before the end of the experiment.


RESULTS
Animals treated with either Dianeal or physiologic saline showed peritoneal membrane thickening and increased vascularity. Fibrosis was demonstrated by increased hydroxyproline concentration. Ultrafiltration was impaired. We found increased concentrations of VEGF and TGFbeta in the peritoneal fluid of animals treated with LPS and daily infusion. Adenovirus-mediated gene transfer to the peritoneal membrane was demonstrated in the model.


CONCLUSIONS
Exposure to LPS and daily Dianeal or physiologic saline leads to peritoneal fibrosis and neoangiogenesis. Vascularization and glucose transport correlate with ultrafiltration failure. The present animal model mimics changes seen in humans on peritoneal dialysis and may be valuable for evaluating short-term interventions to prevent membrane damage.
Margetts
P J
PJ
Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Kolb
M
M
Yu
L
L
Hoff
C M
CM
Gauldie
J
J
D000256:Adenoviridae; D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry; D015314:Dialysis Solutions / Q000008:administration & dosage / Q000737:chemistry*; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000032:analysis; D018014:Gene Transfer Techniques; D008222:Lymphokines / Q000032:analysis; D008297:Male; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015291:Transforming Growth Factors / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D001616:beta-Galactosidase / Q000235:genetics
D015314:Dialysis Solutions; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015291:Transforming Growth Factors; D001616:beta-Galactosidase