Biocompatibility of peritoneal dialysis fluids: long-term exposure of nonuremic rats.
OBJECTIVE
Long-term peritoneal dialysis (PD) leads to structural and functional changes in the peritoneum. The aim of the present study was to investigate the long-term effects of PD fluid components, glucose and glucose degradation products (GDP), and lactate-buffered solution on morphology and transport characteristics in a nonuremic rat model.


METHODS
Rats were subjected to two daily intraperitoneal injections (20 mL/day) during 12 weeks of one of the following: commercial PD fluid (Gambrosol, 4%; Gambro AB, Lund, Sweden), commercial PD fluid with low GDP levels (Gambrosol trio, 4%; Gambro AB), sterile-filtered PD fluid (4%) without GDP, or a glucose-free lactate-buffered PD fluid. Punctured and untreated controls were used. Following exposure, the rats underwent a single 4-hour PD dwell (30 mL, 4% glucose) to determine peritoneal function. Additionally, submesothelial tissue thickness, percentage of high mesothelial cells (perpendicular diameter > 2 microm), vascular density, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF) beta1 mRNA expression were determined. Submesothelial collagen concentration was estimated by van Gieson staining.


RESULTS
Submesothelial tissue thickness and vascular density, mediated by VEGF and TGFbeta production, in the diaphragmatic peritoneum increased significantly in rats exposed to any PD fluid. Gambrosol induced a marked increased fibrosis of the hepatic peritoneum. A significant increase in high mesothelial cells was observed in the Gambrosol group only. Net ultrafiltration was reduced in the Gambrosol and in the glucose-free groups compared to untreated controls. Small solute transport was unchanged, but all groups exposed to fluids showed significantly increased lymph flow.


CONCLUSIONS
Our results show that long-term exposure to different components of PD fluids leads to mesothelial cell damage, submesothelial fibrosis, and neoangiogenesis. Mesothelial cell damage could be connected to the presence of GDP; the other changes were similar for all fluids. Peritoneal transport characteristics did not change in any consistent way and the neoangiogenesis observed was not paralleled by increased solute transport.
Musi
Barbara
B
Department of Nephrology and Physiology, University Hospital of Lund, Sweden. barbara.musi@gambro.com
Braide
Magnus
M
Carlsson
Ola
O
Wieslander
Anders
A
Albrektsson
Ann
A
Ketteler
Markus
M
Westenfeld
Ralf
R
Floege
Jürgen
J
Rippe
Bengt
B
D000818:Animals; D002021:Buffers; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D015312:Hemodialysis Solutions / Q000494:pharmacology*; D007773:Lactates / Q000494:pharmacology*; D008297:Male; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002021:Buffers; D015312:Hemodialysis Solutions; D007773:Lactates; D005947:Glucose