• Shuaijun Ma, Ruochen Qi, Shichao Han, Zhengxuan Li, Xiaoyan Zhang, Guohui Wang, Kepu Liu, Tong Xu, Yang Zhang, Donghui Han, Jingliang Zhang, Di Wei, Xiaozheng Fan, Dengke Pan, Yanyan Jia, Jing Li, Zhe Wang, Xuan Zhang, Zhaoxu Yang, Kaishan Tao, Xiaojian Yang, Kefeng Dou, and Weijun Qin.
• Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
• Chin. Med. J. 2024 Oct 18.

BackgroundThe primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation.MethodsWe conducted a kidney xenotransplantation in a deceased human recipient using a porcine kidney with five gene edits (5GE) on March 25th, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation.ResultsThe combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient.Conclusions5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

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