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The effect of sirolimus in the development of chronic allograft nephropathy
1S.B. Tepecik Teaching Hospital, Organ Transplantation Center, Izmir, Turkey. alpgurkan@superonline.com
Purpose:
The effect of sirolimus (SRL) in renal function was studied in renal transplant recipients.
Patients And Methods:
We studied 20 patients who underwent live related kidney transplantation 1 to 2 years prior under cyclosporine (CsA) treatment and displayed serum creatinine values between 2 and 3 mg/dL. The patients were randomized into 2 groups prospectively. The calcineurin inhibitors (CNI) group continued taking CsA; the SRL group underwent a switch from CsA to SRL. Biopsies were performed to assess chronic allograft nephropathy (CAN) findings and TGFbeta1 in the transplanted kidneys at the beginning and the end of the study. Creatinine clearance, serum creatinine, and proteinuria values were detected in the beginning as well as at 1, 3, 6, and 12 months later.
Results:
At the beginning of the study, the creatinine clearance and serum creatinine levels were 52.21 mL/min and 2.05 mg/dL in the CNI group and 47.76 mL/min and 2.13 mg/dL in the SRL group, respectively. At 12 months, these values were 48.11 mL/min and 2.57 mg/dL in the CNI group and 50.45 mL/min and 2.12 mg/dL in the SRL group, respectively. Creatinine clearance values between the 2 groups at 12 months were statistically different. Although it was not significant, there was a tendency toward decreases inflammatory infiltration and TGFbeta1 levels in the SRL group compared with the CNI group on the second biopsies.
Conclusion:
Pathologic findings of CAN development, serum creatinine, and creatinine clearance values were ameliorated in the SRL group. We concluded that SRL positively affected long-term graft survival.
Insights
Switching from cyclosporine (CsA) to sirolimus (SRL) improved renal function and chronic allograft nephropathy (CAN) in kidney transplant patients. Sirolimus (SRL) positively impacted long-term graft survival.
Area of Science:
- Nephrology
- Transplantation Immunology
Background:
- Chronic allograft nephropathy (CAN) is a significant cause of long-term kidney transplant failure.
- Calcineurin inhibitors (CNIs) like cyclosporine (CsA) are effective immunosuppressants but can contribute to nephrotoxicity.
- Alternative immunosuppressive strategies are needed to improve renal function and graft survival.
Purpose of the Study:
- To evaluate the effect of switching from CsA to sirolimus (SRL) on renal function in kidney transplant recipients with established chronic allograft nephropathy (CAN).
- To compare the impact of SRL versus continued CsA on markers of renal function and histological findings of CAN.
Main Methods:
- A prospective randomized study of 20 kidney transplant recipients with serum creatinine between 2-3 mg/dL.
- Patients were randomized to either continue CsA (CNI group) or switch to SRL (SRL group).
- Renal function (creatinine clearance, serum creatinine, proteinuria) and kidney biopsy findings (CAN, TGF-beta1) were assessed at baseline and 12 months.
Main Results:
- At 12 months, the SRL group showed improved creatinine clearance (50.45 mL/min) and stable serum creatinine (2.12 mg/dL) compared to the CNI group (48.11 mL/min and 2.57 mg/dL).
- Creatinine clearance values were statistically different between groups at 12 months.
- The SRL group exhibited a trend towards decreased inflammatory infiltration and TGF-beta1 levels on repeat biopsies.
Conclusions:
- Switching to sirolimus (SRL) ameliorated pathological findings of chronic allograft nephropathy (CAN) and improved renal function markers.
- Sirolimus (SRL) demonstrated a positive effect on long-term kidney graft survival.
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