Kumar Dhiren, LeCorchick Spencer, Gupta Gaurav
Division of Nephrology, Virginia Commonwealth University, Richmond, VA, USA.
Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA, USA.
Front Med (Lausanne). 2017 May 19;4:60. doi: 10.3389/fmed.2017.00060. eCollection 2017.
The goal of immunosuppression in transplantation has shifted to improving long-term outcomes, reducing drug-induced toxicities while preserving the already excellent short-term outcomes. Long-term gains in solid organ transplantation have been limited at least partly due to the nephrotoxicity and metabolic side effects of calcineurin inhibitors (CNIs). The alloimmune response requires activation of the costimulatory pathway for T cell proliferation and amplification. Belatacept is a molecule that selectively blocks T cell costimulation. In June 2011, the U.S. Food and Drug Administration approved it for maintenance immunosuppression in kidney transplantation based on two open-label, randomized, phase III trials. Since its introduction, belatacept has shown promise in both short- and long-term renal transplant outcomes in several other trials. It exhibits a superior side effect profile compared to CNIs with a comparable efficacy. Across all solid organ transplants, the burden of chronic kidney disease, its associated cardiovascular morbidity, mortality, and inferior patient/allograft survival is a well-documented problem. In this review, we aim to discuss the evidence behind the use of belatacept in solid organ transplants as an effective alternative to CNIs for renal rescue in patients with acute and/or chronic kidney injury.
移植免疫抑制的目标已转向改善长期疗效,在保持已有的出色短期疗效的同时减少药物诱导的毒性。实体器官移植的长期获益有限,至少部分原因是钙调神经磷酸酶抑制剂(CNIs)的肾毒性和代谢副作用。同种免疫反应需要共刺激途径激活才能实现T细胞增殖和扩增。贝拉西普是一种选择性阻断T细胞共刺激的分子。2011年6月,基于两项开放标签、随机、III期试验,美国食品药品监督管理局批准其用于肾移植的维持免疫抑制。自引入以来,贝拉西普在其他多项试验的短期和长期肾移植疗效方面均显示出前景。与CNIs相比,其副作用更小,疗效相当。在所有实体器官移植中,慢性肾脏病负担及其相关的心血管发病率、死亡率以及较差的患者/移植物存活率是一个有充分文献记载的问题。在本综述中,我们旨在讨论贝拉西普用于实体器官移植作为急性和/或慢性肾损伤患者肾挽救中CNIs有效替代方案的证据。