Renal, efficacy and safety outcomes following late conversion of kidney transplant patients from calcineurin inhibitor therapy to everolimus: the randomized APOLLO study

Sirolimus and everolimus in kidney transplantation

“…At their introduction, mTORi were only prescribed in combination with cyclosporine and steroids because a synergistic and different mechanism of action was present compared with CNIs [2,3]. As a result of the damaging effects of cyclosporine on the donor kidney, everolimus has now been extensively tested in the absence of cyclosporine in clinical trials and conversion seems to be successful for improving the estimated glomerular filtration rate (eGFR) [4,5]. Also combined reduced CNI + sirolimus or everolimus regimens have proven their efficacy and safety in a large number of studies.…”

Everolimus immunosuppression in kidney transplantation: What is the optimal strategy?

“…In the APOLLO study, eGFR was significantly higher in the everolimus cohort at one year after conversion, with a mean between-group difference of 4.9mL/min/1.73m 2 (p=0.030) [36]. The ASCERTAIN study showed stable function with or without switch to everolimus to 24 months, but no significant difference in favor of the everolimus-treated cohort [37].…”

“…Overall results thus include a relatively high proportion of patients who converted back to the control regimen. When only those patients who remained on an everolimus-based, CNI-free regimen were analyzed, longterm data after early switch to everolimus in the CENTRAL study [41] or late switch in the APOLLO study [36] showed that conversion resulted in significantly better renal function than a conventional CNI-based regimen.…”

“…These studies excluded patients at high risk for rejection, based on panel reactive antibodies (PRA) level and/or certain types of acute rejection prior to switch. The time post-transplant at which CNI withdrawal was started varied markedly -from seven weeks [33] to a mean of almost seven years [36].…”

“…Several randomized trials have investigated the effect of introducing everolimus and withdrawing CNI therapy in kidney transplant populations with the goal of preserving long-term renal function (Table 2) [27,[33][34][35][36][37]. These studies excluded patients at high risk for rejection, based on panel reactive antibodies (PRA) level and/or certain types of acute rejection prior to switch.…”