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

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.