Yamamoto Takayuki, Pearson Daniel S, Ababneh Emad I, Harris Cynthia, Nissaisorakarn Pitchaphon, Mahowald Grace K, Heher Yael K, Elias Nahel, Markmann James F, Lewis Gregory D, Riella Leonardo V
Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
Front Nephrol. 2022 Nov 28;2:1047217. doi: 10.3389/fneph.2022.1047217. eCollection 2022.
Preformed donor-specific antibodies are associated with a higher risk of rejection and worse graft survival in organ transplantation. However, in heart transplantation, the risk and benefit balance between high mortality on the waiting list and graft survival may allow the acceptance of higher immunologic risk donors in broadly sensitized recipients. Transplanting donor-recipient pairs with a positive complement dependent cytotoxic (CDC) crossmatch carries the highest risk of hyperacute rejection and immediate graft loss and is usually avoided in kidney transplantation. Herein we report the first successful simultaneous heart-kidney transplant with a T- and B-cell CDC crossmatch positive donor using a combination of rituximab, intravenous immunoglobulin, plasmapheresis, bortezomib and rabbit anti-thymocyte globulin induction followed by eculizumab therapy for two months post-transplant. In the year following transplantation, both allografts maintained stable graft function (all echocardiographic left ventricular ejection fractions ≥ 65%, eGFR>60) and showed no histologic evidence of antibody-mediated rejection. In addition, the patient has not developed any severe infections including cytomegalovirus or BK virus infection. In conclusion, a multitarget immunosuppressive regimen can allow for combined heart/kidney transplantation across positive CDC crossmatches without evidence of antibody-mediated rejection or significant infection. Longer follow-up will be needed to further support this conclusion.
预存的供者特异性抗体与器官移植中更高的排斥风险及更差的移植物存活相关。然而，在心脏移植中，等待名单上的高死亡率与移植物存活之间的风险和益处平衡，可能使得在广泛致敏的受者中接受免疫风险更高的供者成为可能。移植补体依赖细胞毒性（CDC）交叉配型阳性的供受者对，发生超急性排斥和即刻移植物丢失的风险最高，在肾移植中通常会避免。在此，我们报告首例成功的心脏-肾脏同时移植，供者的T细胞和B细胞CDC交叉配型均为阳性，采用了利妥昔单抗、静脉注射免疫球蛋白、血浆置换、硼替佐米和兔抗胸腺细胞球蛋白诱导治疗的联合方案，随后在移植后两个月使用依库珠单抗治疗。在移植后的一年里，两个同种异体移植物的功能均保持稳定（所有超声心动图检查的左心室射血分数≥65%，估算肾小球滤过率>60），且未显示抗体介导排斥的组织学证据。此外，患者未发生任何严重感染，包括巨细胞病毒或BK病毒感染。总之，多靶点免疫抑制方案可实现CDC交叉配型阳性的心脏/肾脏联合移植，且无抗体介导排斥或严重感染的证据。需要更长时间的随访来进一步支持这一结论。
