Costimulatory Blockade and Use of mTOR Inhibitors: Avoiding Injury Part 2

Kidney transplantation immunosuppression relies on a calcineurin inhibitor backbone. Calcineurin inhibitors have reduced early-acute rejection rates but failed to improve long-term allograft survival. Their nephrotoxicity has shifted the focus of investigation to calcineurin inhibitor-free regimens. Costimulation blockade with belatacept, a second generation, higher avidity variant of CTLA4-Ig, has emerged as part of a calcineurin inhibitor-free regimen. Belatacept has demonstrated superior glomerular filtration rate compared with calcineurin inhibitors albeit with an increased risk of early and histologically severe rejection. Focus on optimizing the belatacept regimen to reduce the acute rejection rate while maintaining superior renal function is underway. Belatacept has also been utilized as part of a calcineurin inhibitor-free conversion strategy in stable renal transplant recipients and has demonstrated superior improvement in glomerular filtration rate with conversion vs calcineurin inhibitor continuation. Additional work is underway to better define the role of belatacept in patients on calcineurin inhibitors with allograft dysfunction not due to rejection.