Conversion from calcineurin inhibitor–based immunosuppression to mammalian target of rapamycin inhibitors or belatacept in renal transplant recipients

Abstract

The calcineurin inhibitors (CNIs) remain the standard of care for maintenance immunosuppression following renal transplantation. CNIs have demonstrated their effectiveness in reducing acute cellular rejection; however, some evidence suggests that these compounds negatively affect native renal function and are associated with allograft injury in renal transplant recipients. CNIs have also been linked with hypertension, new-onset diabetes after transplantation, tremor, and thrombotic microangiopathy, which have significant consequences for long-term allograft function and patient health overall. Thus, converting patients to a non-CNI-based regimen may improve renal function and also provide extrarenal benefits. A number of studies have been conducted that explore CNI conversion strategies in renal transplant recipients in an effort to improve long-term allograft function and survival. These include converting to alternative, non-nephrotoxic, maintenance immunosuppressants, such as the mammalian target of rapamycin inhibitors (sirolimus and everolimus) and the costimulation blocker belatacept. In this review of literature, evidence for the potential renal and extrarenal benefits of conversion to these non-CNI-based regimens is evaluated. Clinical challenges, including the adverse event profiles of non-CNI-based regimens and the selection of candidates for conversion, are also examined.

Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial

“…3,4 Some CNI-avoiding or CNI-minimizing immunosuppressive regimens, many involving the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus, have been evaluated in kidney transplant recipients. 5 In prospective studies, patients switching from CNI-based to mTOR inhibitor-based immunosuppression showed significant improvements in kidney function at 12 months postconversion versus patients who continue treatment with cyclosporine or tacrolimus. However, mTOR inhibitortreated patients are more likely to have adverse events (AEs), especially dyslipidemia and proteinuria.…”

Sirolimus-based, calcineurin inhibitor- free regimen in kidney transplant patients: An open-label, randomized, controlled trial

“…Eur J Gen Med 2016;13(3): [16][17][18][19][20][21][22] mmHg; P=0.04) in the SRL and Tac groups, respectively. At 36 month, the mean systolic blood pressure (132±19 and 141±21 mmHg; P=0.001) and diastolic blood pressure (74±14 mmHg and 82±10 mmHg; P=0.001) in the SRL and Tac groups, respectively.…”

“…Oral prednisolone was then given at a dose of 1 mg/ kg per day, and then gradually tapered down to 5 mg/day by the 3rd month post-transplantation. Tacrolimus was started at a dose of 0.075 mg/kg/day in two divided doses targeting Eur J Gen Med 2016;13(3): [16][17][18][19][20][21][22] a 12-h whole blood trough level of 10-15 ng/mL in the first 3 months and then from 3 to 7 ng/ml thereafter. Concomitant immunosuppression and other treatments (i.e.…”

“…It may also have a role as an effective substitute for CNI therapy late after transplantation to avoid further CNI nephrotoxicity (18)(19)(20)(21)(22)(23). However, the potential risk and benefit of this conversion strategy is not yet fully known, especially in the long term.…”

Efficacy and safety of early tacrolimus conversion to sirolimus after kidney transplantation: Long-term results of a prospective randomized study

“…[161718] It may also have a role as an effective substitute for CNI therapy late after transplantation to avoid further CNI nephrotoxicity. [192021222324] However, the potential risk and benefit of this conversion strategy are not yet fully known, especially in the long-term.…”