Wojciechowski David, Vincenti Flavio
Division of Nephrology, Massachusetts General Hospital, Boston, MA; and Kidney Transplant Service, University of California, San Francisco, CA.
Division of Nephrology, Massachusetts General Hospital, Boston, MA; and Kidney Transplant Service, University of California, San Francisco, CA.
Adv Chronic Kidney Dis. 2016 Sep;23(5):306-311. doi: 10.1053/j.ackd.2016.09.004.
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.
肾移植免疫抑制依赖于以钙调神经磷酸酶抑制剂为基础的方案。钙调神经磷酸酶抑制剂降低了早期急性排斥反应的发生率，但未能提高长期移植肾的存活率。它们的肾毒性已将研究重点转移到无钙调神经磷酸酶抑制剂的方案上。使用贝拉西普进行共刺激阻断，贝拉西普是第二代、亲和力更高的CTLA4-Ig变体，已成为无钙调神经磷酸酶抑制剂方案的一部分。与钙调神经磷酸酶抑制剂相比，贝拉西普已显示出更高的肾小球滤过率，尽管早期和组织学上严重排斥反应风险增加。目前正在致力于优化贝拉西普方案，以降低急性排斥反应发生率，同时维持良好的肾功能。贝拉西普也已被用作稳定肾移植受者无钙调神经磷酸酶抑制剂转换策略方案的一部分，并且与继续使用钙调神经磷酸酶抑制剂相比，转换后在肾小球滤过率方面显示出更显著的改善。正在开展更多工作，以更好地明确贝拉西普在因非排斥原因导致移植肾功能不全的钙调神经磷酸酶抑制剂治疗患者中的作用。
