Physiologic Homeostasis in a Living Human after Pig Kidney Xenotransplantation

Sul A Lee, Marie-Camille Lafargue, Winfred W. Williams, Kassem Safa, Ragnar Palsson, Ayman Al Jurdi, Abraham Cohen-Bucay, Pitchaphon Nissaisorakarn, Hannah Gilligan, Harald Jüeppner, Leela Morena, Thiago J. Borges, Mariesa A. Le, Kayla F. Joyal, Eugene P. Rhee, Ivy Rosales, Thomas Brannon, Jan Wysocki, Daniel Batlle, Tatsuo Kawai and Leonardo V. Riella ()
Additional contact information
Sul A Lee: Massachusetts General Hospital
Marie-Camille Lafargue: Massachusetts General Hospital
Winfred W. Williams: Massachusetts General Hospital
Kassem Safa: Massachusetts General Hospital
Ragnar Palsson: Massachusetts General Hospital
Ayman Al Jurdi: Massachusetts General Hospital
Abraham Cohen-Bucay: Massachusetts General Hospital
Pitchaphon Nissaisorakarn: Massachusetts General Hospital
Hannah Gilligan: Massachusetts General Hospital
Harald Jüeppner: Harvard Medical School
Leela Morena: Massachusetts General Hospital
Thiago J. Borges: Massachusetts General Hospital
Mariesa A. Le: Massachusetts General Hospital
Kayla F. Joyal: Massachusetts General Hospital
Eugene P. Rhee: Massachusetts General Hospital
Ivy Rosales: Harvard Medical School
Thomas Brannon: Northwestern University Feinberg School of Medicine
Jan Wysocki: Northwestern University Feinberg School of Medicine
Daniel Batlle: Northwestern University Feinberg School of Medicine
Tatsuo Kawai: Massachusetts General Hospital
Leonardo V. Riella: Massachusetts General Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-63153-3

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