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Published on: May 2, 2013
Protective effects of sirolimus by attenuating connective tissue growth factor expression in human chronic allograft
1Department of Kidney Transplantation, Nanjing Medical University, First Affiliated Hospital, Guangzhou Road 300, Nanjing, Jiangsu 210029, China. lucky_lm@263.net
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.
Insights
Converting to sirolimus (RAPA) improved graft survival and function in patients with chronic allograft nephropathy (CAN). This treatment stabilized CAN grading and reduced connective tissue growth factor (CTGF) expression, unlike cyclosporine (CsA) reduction.
Area of Science:
- Nephrology
- Transplantation Immunology
- Pharmacology
Background:
- Chronic allograft nephropathy (CAN) significantly impacts renal transplant outcomes.
- Sirolimus (RAPA) offers a potential therapeutic strategy, particularly with reduced cyclosporine (CsA) dosages.
- Investigating sirolimus conversion's efficacy in biopsy-proven CAN is crucial.
Purpose of the Study:
- To evaluate the effects of sirolimus conversion versus CsA reduction on renal transplant recipients with biopsy-proven CAN.
- To assess the impact on graft function, survival rates, and histological markers of fibrosis.
Main Methods:
- A randomized trial involving 110 renal transplant recipients with biopsy-proven CAN.
- Participants were assigned to either CsA reduction (n=54) or sirolimus conversion (n=56).
- Outcomes were assessed over 24 months, including graft function, survival, CAN Banff grading, and intrarenal CTGF expression.
Main Results:
- Sirolimus conversion led to significantly better graft function and survival rates compared to CsA reduction.
- CAN Banff grading remained stable in the sirolimus group but worsened in the CsA group.
- Sirolimus treatment attenuated intrarenal connective tissue growth factor (CTGF) expression, unlike CsA.
Conclusions:
- Sirolimus conversion is a beneficial strategy for improving long-term graft survival in patients with CAN.
- The observed benefits may be linked to sirolimus's antifibrotic and antiproliferative effects, potentially mediated by reduced CTGF expression.
