Lee Sul A, Lafargue Marie-Camille, Williams Winfred W, Safa Kassem, Palsson Ragnar, Al Jurdi Ayman, Cohen-Bucay Abraham, Nissaisorakarn Pitchaphon, Gilligan Hannah, Jüeppner Harald, Morena Leela, Borges Thiago J, Le Mariesa A, Joyal Kayla F, Rhee Eugene P, Rosales Ivy, Brannon Thomas, Wysocki Jan, Batlle Daniel, Kawai Tatsuo, Riella Leonardo V
Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA.
Nat Commun. 2025 Sep 26;16(1):8453. doi: 10.1038/s41467-025-63153-3.
Kidney allotransplantation remains the preferred treatment for end-stage kidney disease, yet donor shortages limit its availability. Xenotransplantation using genetically modified porcine kidneys offers a promising alternative. Here, we report key physiological observations from the first-in-human porcine kidney xenograft over a 51 day postoperative follow-up period. The transplanted kidney maintained essential functions, including waste excretion, electrolyte regulation, and production of concentrated urine, while supporting blood pressure and sodium reabsorption despite reduced activation of the renin-angiotensin-aldosterone system. Sodium retention required diuretic therapy, and mild hypocalcemia and hyperphosphatemia occurred in the setting of pre-existing hypoparathyroidism. Markedly increased urinary uric acid excretion led to hypouricemia without evidence of urate nephropathy. This case demonstrates the ability of a porcine kidney to sustain vital metabolic functions in a living human, while highlighting areas for further research. These findings provide a foundation for optimizing post-transplant care and advancing xenotransplantation as a solution to the critical organ shortage.
肾脏同种异体移植仍然是终末期肾病的首选治疗方法,但供体短缺限制了其可及性。使用基因编辑猪肾脏进行异种移植提供了一种有前景的替代方案。在此,我们报告了首例人类猪肾脏异种移植术后51天随访期内的关键生理学观察结果。移植的肾脏维持了基本功能,包括废物排泄、电解质调节和浓缩尿液生成,同时尽管肾素-血管紧张素-醛固酮系统激活减少,但仍支持血压和钠重吸收。钠潴留需要利尿剂治疗,并且在存在甲状旁腺功能减退的情况下发生了轻度低钙血症和高磷血症。尿尿酸排泄显著增加导致低尿酸血症,且无尿酸盐肾病证据。该病例证明了猪肾脏在活人身上维持重要代谢功能的能力,同时突出了进一步研究的领域。这些发现为优化移植后护理以及推动异种移植作为解决关键器官短缺问题的方案奠定了基础。