Physiologic Homeostasis in a Living Human after Pig Kidney Xenotransplantation
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.
Authors
- Timothy S. Brannon
- Hannah Gilligan
- Thiago J. Borges (ORCID: https://orcid.org/0000-0002-6554-0169)
- Marie-Camille Lafargue (ORCID: https://orcid.org/0000-0001-9000-1207)
- Daniel Batlle (ORCID: https://orcid.org/0000-0002-5878-9046)
- Winfred W. Williams (ORCID: https://orcid.org/0000-0001-9984-7102)
- Harald Jüeppner
- Tatsuo Kawai (ORCID: https://orcid.org/0000-0002-6900-4603)
- Jan Wysocki (ORCID: https://orcid.org/0000-0002-8429-272X)
- Ivy A. Rosales (ORCID: https://orcid.org/0000-0003-0621-3202)
- Pitchaphon Nissaisorakarn (ORCID: https://orcid.org/0000-0002-0245-2954)
- Eugene P. Rhee (ORCID: https://orcid.org/0000-0002-4804-7583)
- Mariesa A. Le (ORCID: https://orcid.org/0000-0002-5220-7228)
- Kayla Joyal
- Kassem Safa (ORCID: https://orcid.org/0000-0002-9283-7662)
- Leela Morená (ORCID: https://orcid.org/0000-0001-8295-1026)
- Ragnar Pálsson (ORCID: https://orcid.org/0000-0002-7104-9296)
- Leonardo V. Riella (ORCID: https://orcid.org/0000-0002-7636-3196)
- Abraham Cohen‐Bucay (ORCID: https://orcid.org/0000-0003-4951-7070)
- Sul A Lee (ORCID: https://orcid.org/0000-0003-2121-721X)
- Ayman Al Jurdi (ORCID: https://orcid.org/0000-0002-7957-137X)
Institutions
- Northwestern University (US)
- Centre National de la Recherche Scientifique (FR)
- Harvard University (US)
- Inserm (FR)
- Université Paris Cité (FR)
- Institut Necker Enfants Malades (FR)
- Massachusetts General Hospital (US)
- Center for Systems Biology (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-26
- DOI
- https://doi.org/10.1038/s41467-025-63153-3
- Citations
- 7
- Primary Topic
- Xenotransplantation and immune response
- Type
- article
- Field-Weighted Citation Impact
- 14.04
Funders
- Massachusetts General Hospital
- Alexion Pharmaceuticals
- National Institutes of Health