Protective effects of sirolimus by attenuating connective tissue growth factor expression in human chronic allograft nephropathy.
BACKGROUND
Chronic allograft nephropathy (CAN) remains a great challenge for the transplant clinician. The introduction of sirolimus (RAPA) with cyclosporine (CsA) reduction maybe shed new light to improve graft survival. The aim of this study was to investigate the overall effects of sirolimus conversion on biopsy-proven CAN.


METHODS
One hundred and ten renal transplant recipients with biopsy-proven CAN were randomized into two groups: 54 for CsA reduction and 56 for sirolimus conversion treatment. After 24-month follow-up, the outcome variables included graft function and survival as well as CAN Banff grading and intrarenal expression of connective tissue growth factor (CTGF) via repeated biopsy.


RESULTS
Graft function and survival rate were significantly better in the RAPA group. CAN grading worsened in the CsA group, whereas they were stable in the RAPA group. There was weak expression in the RAPA group but significant, increased expression of CTGF in glomeruli and interstitial area in the CSA group (P < .01) both by immunohistochemical staining or real-time polymerase chain reaction detection.


CONCLUSIONS
Sirolimus conversion provided a beneficial strategy to improve long-term graft survival in CAN. Attenuation of renal CTGF expression may be one of its antifibrotic and antiproliferation effects.
Liu
M
M
Department of Kidney Transplantation, Nanjing Medical University, First Affiliated Hospital, Guangzhou Road 300, Nanjing, Jiangsu 210029, China. lucky_lm@263.net
Zhang
W
W
Gu
M
M
Yin
C
C
Zhang
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Q
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Xu
D
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D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002908:Chronic Disease; D055513:Connective Tissue Growth Factor; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D016030:Kidney Transplantation / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008297:Male; D020123:Sirolimus / Q000627:therapeutic use*; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome
C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D007166:Immunosuppressive Agents; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor; D016572:Cyclosporine; D020123:Sirolimus