Protective effects of sirolimus by attenuating connective tissue growth factor expression in human chronic allograft nephropathy

Abstract

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.

Conclusion: 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.