Supplemental administrative effect of everolimus with reduction of calcineurin inhibitors on maintenance kidney transplant recipients

Abstract

Although improvement of kidney graft survival within 5-years after transplantation has been achieved over 95％, chronic graft deterioration still remains against long-term better survival. As chronic nephrotoxicity of calcineurin inhibitors (CNIs) is one of the major causes of chronic graft injury, minimization of CNIs with administration of everolimus (EVR), an mTOR inhibitor, is expected to relieve the toxic effect on the kidney. The aim of this preliminary study was to evaluate the availability and safety of EVR for kidney transplant patients in the maintenance phase. Materials and methods : Fifty-six kidney transplant recipients recieving CNI-based immunosuppression (30 tacrolimus and 26 ciclosporin) with pathologically CNI toxicity and/or interstitial fibrosis/ tubular atrophy (IF/TA) were included. Conversion of immunosuppression was accomplished by reducing the CNIs by 40％ and beginning EVR at 1mg, while the doses of mycophenolate mofetil and steroid remained unchanged. Blood concentration of CNIs and EVR, as well as graft function were examined, and adverse effects were evaluated. Results : The blood concentration of tacrolimus was reduced from 5.3 to 3.3ng/mL (38％ reduction), while that of ciclosporin was reduced from 137 to 79ng/mL (42％). The concentration of EVR was 2.7ng/mL in tacrolimus patients and 3.9ng/mL in cyclosporine patients. Improvement of graft function at 3 months after beginning EVR administration was observed as a 13％ increase in eGFR (41 to 46mg/dL). Furthermore, 20％ of the patients showed an increase in urine protein excretion. Although 46％ of patients experienced stomatitis, most gradually recovered. Conclusion：Immunosuppression conversion by supplemental administration of EVR along with significant reduction in CNIs was found to improve graft function in maintenance phase of kidney transplant recipients.