Comparison of early and late conversion of sirolimus in experimental model of chronic cyclosporine nephropathy.
Sirolimus (SRL) is a promising drug for replacing calcineurin inhibitors. We performed this study to determine the optimal time of conversion from cyclosporine (CsA) to SRL in an experimental model of chronic CsA nephropathy. Three separate studies were performed. In the first study, SRL was given to rats with or without CsA for 4 weeks. In the second study, rats were treated initially with CsA for 1 week, and then switched to SRL (early conversion). In the third study, CsA was given for 4 weeks and then replaced by SRL for 4 weeks treatment of CsA (late conversion). The influence of SRL on CsA-induced renal injury was evaluated by assessing renal function, histopathology (interstitial inflammation and fibrosis), and apoptotic cell death. Combined CsA and SRL treatment significantly impaired renal function, increased apoptosis, and interstitial fibrosis and inflammation compared with CsA or SRL treatment alone. Early conversion to SRL did not change renal function, histopathology, or apoptosis compared with early CsA withdrawal. By contrast, late conversion to SRL significantly aggravated these parameters compared with late CsA withdrawal. In conclusion, early conversion from CsA to SRL is effective in preventing CsA-induced renal injury in a setting of CsA-induced renal injury.
Transplant Research Center, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea, Seoul, Korea.
Jin Young
JY
Kim
Jung Yeon
JY
Ghee
Sun Woo
SW
Lim
Shang Guo
SG
Piao
Byung Ha
BH
Chung
Hye Eun
HE
Yoon
Hyeon Seok
HS
Hwang
Bum Soon
BS
Choi
Jin
J
Kim
Chul Woo
CW
Yang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002908:Chronic Disease; D016572:Cyclosporine / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus