Introduction of everolimus in kidney transplant recipients at a late posttransplant stage

Abstract

This minireview focuses on the current knowledge about the introduction of everolimus (EVL), a mammalian target of rapamycin inhibitor, with calcineurin inhibitor (CNI) elimination or minimization in kidney transplant recipients at a late posttransplant stage. Within, we have summarized two major clinical trials, ASCERTAIN and APOLLO, and seven other retrospective or nonrandomized studies. In the open-label multicenter ASCERTAIN study, the estimated glomerular filtration rate (eGFR) at 24 mo after conversion was not significantly different between three groups-EVL with CNI elimination, CNI minimization and continued CNI unchanged-at a mean of 5.4 years after transplantation. However, recipients with baseline creatinine clearance higher than 50 mL/min had a greater increase in measured GFR after CNI elimination. In the open-label multicenter APOLLO study, adjusted eGFR within the on-treatment population was significantly higher in the EVL continuation group than in the CNI continuation group at 12 mo after conversion at a mean of 7 years posttransplantation. Other studies on recipients without adverse events and already having satisfactory renal function showed favorable graft function by EVL late-induction with CNI elimination or reduction. These studies showed that chronic allograft nephropathy, CNI nephrotoxicity, CNI arteriolopathy, cancer and viral infection (especially cytomegalovirus infection) may be good indications for late conversion to EVL.

Keywords: Kidney transplantation; Everolimus; mTOR inhibitor; Late conversion; Calcineurine inhibitor

Core tip: Current immunosuppressive protocols consisting of calcineurin inhibitors (CNIs) and mycophenolate mofetil have improved short-term graft survival. However, improvements in long-term graft survival are restricted by nephrotoxicity associated with CNI. Everolimus is an exceedingly useful immunosuppressant for kidney transplant recipients when administered in combination with low-dose CNIs or with elimination of CNIs. Here, we summarize the current knowledge about the introduction of everolimus with CNI elimination or minimization in kidney transplant recipients at late posttransplant stage.