NYU Langone Transplant Institute, NYU Langone Health, New York, New York, USA.
Curr Opin Nephrol Hypertens. 2023 Mar 1;32(2):193-198. doi: 10.1097/MNH.0000000000000858. Epub 2022 Nov 17.
The greatest challenge facing end-stage kidney disease (ESKD) patients is the scarcity of transplantable organs. Advances in genetic engineering that mitigate xenogeneic immune responses have made transplantation across species a potentially viable solution to this unmet need. Preclinical studies and recent reports of pig-to-human decedent renal xenotransplantation signify that clinical trials are on the horizon. Here, we review the physiologic differences between porcine and human kidneys that could impede xenograft survival. Topics addressed include porcine renin and sodium handling, xenograft water handling, calcium, phosphate and acid-base balance, responses to porcine erythropoietin and xenograft growth.
Studies in nonhuman primates (NHPs) have demonstrated that genetically modified pig kidneys can survive for an extended period when transplanted into baboons. In recent studies conducted by our group and others, hyperacute rejection did not occur in pig kidneys lacking the α1,3Gal epitope transplanted into brain-dead human recipients. These experimental trials did not study potential clinical abnormalities arising from idiosyncratic xenograft responses to human physiologic stimuli due to the brief duration of observation this model entails.
Progress in biotechnology is heralding an era of xenotransplantation. We highlight the physiologic considerations for xenogeneic grafts to succeed.
终末期肾病（ESKD）患者面临的最大挑战是可移植器官的稀缺。减轻异种免疫反应的基因工程进展使跨物种移植成为满足这一未满足需求的潜在可行解决方案。猪到人体死亡肾异种移植的临床前研究和最近报告标志着临床试验即将到来。在这里，我们回顾了可能阻碍异种移植物存活的猪和人肾脏之间的生理差异。讨论的主题包括猪肾素和钠处理、异种移植物水管理、钙、磷和酸碱平衡、对猪促红细胞生成素的反应和异种移植物生长。
在非人类灵长类动物（NHPs）中的研究表明，当将经过基因改造的猪肾脏移植到狒狒中时，它们可以在很长一段时间内存活。在我们小组和其他小组进行的最近研究中，缺乏α1,3Gal 表位的猪肾脏在移植到脑死亡的人类受者中没有发生超急性排斥反应。由于该模型所涉及的观察时间短暂，这些实验性试验并未研究由于人类生理刺激引起的异种移植物反应的特殊性而导致的潜在临床异常。
生物技术的进步预示着异种移植的时代即将到来。我们强调了异种移植物成功的生理考虑因素。
