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Immunosuppression Modification by Everolimus With Minimization of Calcineurin Inhibitors Recovers Kidney Graft
M Nojima1, Y Yamada1, Y Higuchi2
1Kidney Transplant Center and Department of Urology, Hyogo College of Medicine, Hyogo, Japan.
Background:
Although kidney graft survival within 5 years after transplantation is now achieved in >95% of recipients, chronic graft deterioration remains a factor limiting long-term survival. Chronic nephrotoxicity induced by calcineurin inhibitors (CNIs) is one of the major causes of chronic graft injury; thus, minimization of CNIs by administration of everolimus (EVR) is expected to relieve their toxic effects.
Methods:
Fifty-six kidney transplant recipients receiving CNI-based immunosuppression (tacrolimus, n = 34; cyclosporine, n = 22) were analyzed. The average posttransplant period at conversion was 7.4 years and no less than 3 years. Conversion of immunosuppression was accomplished by reducing CNI by 40% in dose and beginning EVR at 1 or 1.5 mg. Changes in graft function were examined, and adverse effects were evaluated.
Results:
Significant improvement in graft function was observed quickly after EVR administration, and it had persisted for 1 year after conversion as a 7% increase in estimated glomerular filtration rate. No obvious acute rejection was observed. Further analyses concerning "timing of EVR conversion" and "graft function at conversion" were performed. Graft function was significantly improved even in patients with late conversion at 2 to 10 years. The estimated glomerular filtration rate was significantly improved even in patients with poor function.
Conclusions:
We concluded that this modification to the immunosuppressive regimen, as expected, reduced CNI nephrotoxicity. Our results showed that even patients with very late conversion or poor graft function also benefited from EVR conversion with CNI minimization.
Insights
Minimizing calcineurin inhibitors (CNIs) with everolimus (EVR) improves kidney transplant graft function. This strategy benefits patients even with late conversion or poor initial graft function, reducing CNI nephrotoxicity.
Area of Science:
- Nephrology
- Immunosuppression
- Transplantation
Background:
- Chronic graft deterioration limits long-term kidney transplant survival.
- Calcineurin inhibitor (CNI) nephrotoxicity is a major cause of chronic graft injury.
- Minimizing CNIs with everolimus (EVR) may reduce CNI-induced toxic effects.
Purpose of the Study:
- To evaluate the efficacy of CNI minimization using EVR in kidney transplant recipients.
- To assess the impact of EVR conversion on graft function and nephrotoxicity.
- To determine if conversion timing or baseline graft function affects EVR benefits.
Main Methods:
- Fifty-six kidney transplant recipients on CNI-based immunosuppression were analyzed.
- CNI dosage was reduced by 40% and EVR was initiated (1 or 1.5 mg).
- Graft function and adverse effects were monitored post-conversion.
Main Results:
- A 7% increase in estimated glomerular filtration rate (eGFR) was observed within 1 year post-conversion.
- Significant graft function improvement occurred regardless of conversion timing (2-10 years post-transplant).
- Patients with poor initial graft function also showed significant eGFR improvement.
Conclusions:
- Reducing CNI dosage and adding EVR effectively minimizes CNI nephrotoxicity.
- EVR conversion offers benefits for graft function, even in late-stage or compromised kidney transplants.
- This immunosuppression modification strategy enhances long-term graft survival prospects.
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