The role of the TGF/Smad signaling pathway in peritoneal fibrosis induced by peritoneal dialysis solutions.
BACKGROUND
Peritoneal dialysis (PD) solutions contribute to peritoneal membrane damage. We investigated how conventional and biocompatible PD solutions with different glucose concentrations affect morphological and functional signs of peritoneal fibrosis as well as the TGF-beta1/Smad signaling pathway in a chronic PD rat model.


METHODS
Non-uremic male Wistar rats (n = 28) were dialyzed thrice daily for 28 days with 20 ml of a conventional solution (Dianeal 1.36%, D1, or 3.86%, D3) or a biocompatible solution (Physioneal 1.36%, P1, or 3.86%, P3). A peritoneal equilibration test was performed. Six rats without dialysis served as controls.


RESULTS
The use of conventional solutions, particularly D3, resulted in expansion of the submesothelial compact zone, loss of mesothelial cell layer integrity, hypercellularity, accumulation of collagen I, increased vessel numbers and increased TGF-beta1/Smad expression, but this did not significantly change fluid and solute peritoneal transport characteristics. In comparison with D1 and D3, the use of P1 and P3 was associated with less TGF-beta1/Smad expression and less expansion of the submesothelial cell layer.


CONCLUSIONS
Our findings indicate that biocompatible solutions with less glucose may decrease the rate of peritoneal fibrosis. The TGF-beta1/Smad pathway is stimulated by PD solutions, representing a plausible pathophysiological mechanism.
Yao
Qiang
Q
Divisions of Baxter Novum and Renal Medicine, Department of Clinical Science, Karolinska Institutet, Stockholm, Sweden.
Pawlaczyk
Krzysztof
K
Ayala
Ernesto Rodríguez
ER
Styszynski
Arkadiusz
A
Breborowicz
Andrzej
A
Heimburger
Olof
O
Qian
Jia Qi
JQ
Stenvinkel
Peter
P
Lindholm
Bengt
B
Axelsson
Jonas
J
D000818:Animals; D015314:Dialysis Solutions / Q000009:adverse effects*; D005355:Fibrosis / Q000378:metabolism; D008297:Male; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010532:Peritoneal Diseases / Q000378:metabolism* / Q000473:pathology; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D015314:Dialysis Solutions; D051785:Smad Proteins; D016211:Transforming Growth Factor alpha