Pig Kidney Survives 61 Days in Human Recipient After Rejection Blocked
New studies reveal how to stop immune attacks on transplanted pig organs — and hint at applications for living patients.
Scientists have reported the longest-known survival of a genetically modified pig kidney in a human — 61 days in a brain-dead 57-year-old man in the United States. The success, described in two coordinated Nature papers, offers the clearest evidence so far that immune rejection of pig organs can be reversed and controlled. The findings could help advance xenotransplantation from experimental use in deceased individuals to clinical use in living patients.
The research teams identified key molecular pathways involved in rejection, used targeted therapies to halt immune attacks, and demonstrated that only a single genetic modification to the donor pig may be sufficient to prevent immediate, catastrophic rejection.
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A Rare Window Into Rejection — and How to Stop It
The procedure was performed on 14 July 2023 at New York University Langone. The donor organs — a kidney and a thymus — came from a pig engineered by Revivicor (a subsidiary of United Therapeutics). Only one gene, GGTA1, was removed to eliminate α-gal, a sugar known to trigger rapid rejection in primate xenotransplants.
The kidney functioned immediately after transplantation, producing urine and showing normal perfusion. But on day 33, the organ abruptly deteriorated. Biopsy results revealed antibody-mediated rejection. Physicians intervened with:
Plasma exchange
Steroids
Pegcetacoplan, a complement inhibitor that prevents immune tagging of foreign cells
The kidney stabilized, but on day 49 another rejection episode emerged, this time dominated by an inflammatory cell infiltrate. A T-cell–depleting immunosuppressant reversed the process and restored full kidney function. The planned endpoint of the study was day 61.
“This is the first direct evidence of how rejection can be reversed,” said Muhammad Mohiuddin, a xenotransplantation specialist at the University of Maryland School of Medicine and lead scientist on the first pig-to-human heart transplant (2022).
The Thymus: A Possible Key to Long-Term Tolerance
The research also suggests a central role for the pig thymus, transplanted alongside the kidney. The thymus “educates” T cells, and the authors argue that presenting pig antigens in this context may have helped the recipient’s immune system recognize the organ as permissible rather than foreign.
Robert Montgomery, senior author on one of the Nature papers and director of the NYU Langone Transplant Institute, noted that pig kidneys have historically survived longer in primates when transplanted together with a thymus graft.
What the Immune System Revealed
Molecular analysis of the recipient’s blood and kidney tissue showed:
Rising expression of rejection-associated genes (CXCL9, CXCL10, CXCL11) before treatment
Decreased expression after rejection was reversed
High levels of macrophages and natural killer T cells during the rejection spike on day 33
These findings reinforce the idea that T cells may play an even larger role in xenograft rejection than previously recognized, motivating earlier and more sophisticated monitoring in future clinical attempts.
According to Mohiuddin, molecular blood monitoring could allow clinicians to detect rejection earlier — possibly before structural damage to the organ occurs.
Is One Genetic Edit Enough?
Today, most xenotransplantation research relies on pigs engineered with over ten gene edits to reduce rejection and prevent viral transmission. But these studies suggest that removing only GGTA1 may be enough to prevent hyperacute rejection in carefully controlled conditions.
Montgomery notes that pigs with a single edit can be bred normally, whereas heavily engineered pigs must be cloned — a barrier to wider clinical adoption. Still, the authors caution that additional studies in both brain-dead and living humans will be required to validate this lower-edit strategy.
The same GGTA1-knockout kidney has already been transplanted into one living patient; it failed after two months due to that person’s pre-existing heart failure, making interpretation difficult.
Outlook: Toward Living Patients
Both research groups are collaborating with United Therapeutics on early clinical trials. The new molecular data, combined with the reversal of two distinct rejection episodes, marks a step toward testing pig organs in living individuals with end-stage organ failure.
If validated, xenotransplantation could eventually help address the persistent global shortage of donor organs — a need that grows every year.