Comparison of Early and Late Conversion of Sirolimus in Experimental Model of Chronic Cyclosporine Nephropathy
Journal of Korean Medical Science
;
: 160-169, 2012.
Article
in English
| WPRIM
| ID: wpr-156439
ABSTRACT
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Chronic Disease
/
Cyclosporine
/
Rats, Sprague-Dawley
/
Apoptosis
/
Sirolimus
/
Models, Animal
/
Immunosuppressive Agents
/
Intestines
/
Kidney Diseases
Limits:
Animals
Language:
English
Journal:
Journal of Korean Medical Science
Year:
2012
Type:
Article
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