Plasma exchange and intravenous immunoglobulin prolonged the survival of a porcine kidney xenograft in a sensitized, brain-dead human recipient

作者：Shuaijun Ma, Ruochen Qi, Shichao Han, Zhengxuan Li, Xiaoyan Zhang, Guohui Wang, Kepu Liu, Tong Xu, Zhang Yang, Donghui Han, Jingliang Zhang, Di Wei, Xiaozheng Fan, Dengke Pan, Yanyan Jia, Jing Li, Zhe Wang, Xuan Zhang, Zhao-Xu Yang, Kaishan Tao, Xiaojian Yang, Kefeng Dou, Weijun Qin · 发表于：Chinese Medical Journal · 年份：2024 · DOI：10.1097/cm9.0000000000003338 · 被引用次数：9 · 研究领域：Xenotransplantation and immune response、Animal Genetics and Reproduction、Tissue Engineering and Regenerative Medicine

BACKGROUND: The 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. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 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. RESULTS: The 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 cyt...