Long-Term Results in Recipients of Late Conversion to a Calcineurin Inhibitor-Free Regimen with Everolimus After Kidney Transplantation

Background. Conversion to a calcineurin inhibitor (CNI)-free regimen in cases of CNI nephrotoxicity (CNIT) is a strategy to improve the long-term outcomes of kidney transplantation. However, the long-term results of late conversion to a CNI-free regimen using everolimus (EVR) remain uncertain.Methods. Nine kidney transplant recipients with biopsy-confirmed CNIT were enrolled. The median time of CNIT diagnosis was 9.0 years. All recipients underwent a conversion from CNI to EVR. We evaluated the clinical outcomes, development of donor-specific antibody (DSA), the incidence of rejection, alternative arteriolar hyalinosis (aah) scores, renal function changes, and T cell responses by mixed lymphocyte reaction (MLR) assay after conversion. Results. The median follow-up after conversion was 5.4 years. Currently, 7 of 9 recipients have received a CNI-free regimen for 1.6 to 9.5 years. In the other 2 recipients, one experienced graft loss due to CNIT 3.8 years after conversion, and the other had to resume CNI due to acute T cell-mediated rejection (ATMR) a year after conversion. None of the recipients developed DSA. No rejection was observed in the kidney allograft histology except for the ATMR case. Moreover, improvement in aah scores was noted in one patient. Furthermore, serum creatinine levels were stable in recipients without proteinuria before the EVR add-on. In the MLR analysis, low responses against donors were observed in stable patients. Conclusions. Late conversion to an EVR-based regimen without CNI may be a promising therapeutic strategy against CNIT, particularly for recipients without proteinuria before the EVR add-on.