This Pig Kidney Worked in a Human for 61 Days – Here’s What We Learned
A single-edit pig kidney functioned for 61 days in a brain-dead human recipient.
The shortage of donor kidneys continues to leave thousands of patients without treatment options.
Now, researchers at Columbia University and NYU Langone Health have shown that a minimally edited pig kidney can function in a human body for more than two months.
Xenotransplantation offers new hope
End-stage renal disease affects over 800,000 people in the US, yet only a small fraction receive a transplant each year.
Organ scarcity limits treatment, prompting researchers to explore xenotransplantation, transplanting organs from other species, as a potential solution. Gene-edited pigs are particularly promising due to their practicality for breeding, and their organs are similar in size to humans.
Most progress so far has come from work in non-human primates, where pig kidneys survive longer with gene edits and strong immune suppression, including drugs that block the CD40 pathway. However, animal studies cannot fully replicate human immune responses.
CD40 pathway
The CD40 pathway is an immune signaling route that helps activate T and B cells, playing a key role in organ rejection.
A few teams have transplanted pig kidneys into recently deceased human donors for short periods, three to seven days, which only provides a limited insight into how the human immune system reacts over time or how the kidney performs physiologically.
The new study extended the monitoring period to over two months to address these gaps.
Pig kidney and thymus transplant in a brain-dead recipient
The study involved a 57-year-old man who had been declared brain-dead. Surgeons removed both native kidneys and transplanted a single α-Gal knockout pig kidney along with the donor pig’s thymus, which had been placed under the kidney capsule. The pig organ had only a single genetic modification, and no advanced CD40-pathway immune blockers were used.
α-Gal knockout pig kidney
An α-Gal knockout pig kidney is a pig kidney engineered to remove a sugar molecule called α-Gal that triggers an immediate human immune attack.
Throughout the study, the team carried out frequent sampling, including kidney biopsies, blood analysis, T-cell receptor sequencing, single-cell RNA sequencing and detailed histology.
“We obtained an unprecedented number of tissue, blood and fluid samples from the recipient, allowing us to monitor immunological changes over time and identify ways to improve the success of xenotransplantation,” said corresponding author Dr. Megan Sykes, the Michael J. Friedlander Professor of Medicine and professor of microbiology, immunology and surgical sciences and the director of the Columbia Center for Translational Immunology.
The recipient remained stable for 61 days on standard immunosuppressive drugs.
The kidney produced urine immediately, maintained electrolyte balance and could concentrate urine in response to human vasopressin.
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“One of the kidneys’ jobs is to keep proteins in the body and prevent their release into urine. With the thymo-kidney transplant, we saw no evidence of this complication,” said Sykes.
Some hormonal functions did not carry over, including renin, aldosterone and erythropoietin production. Phosphate handling was also limited, leading to high phosphate levels.
Early immune activity appeared in the first month, with natural killer cells and macrophages present in the kidney tissue along with IgM and IgA deposits and signs of complement activation.
However, these changes did not affect function.
On day 33, antibody-mediated rejection was detected, later combined with T-cell activity.
“These antibodies are directed at other unknown pig antigens, and I think it will be really important to identify them to improve future xenotransplants,” said Sykes.
However, the thymus addition seemed to have some moderating effect on immune response, restraining attacks on the kidney.
“Our analyses suggested that the transplanted pig thymus may have helped to restrain the recipient’s immune system from attacking the kidney,” Sykes explained.
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The rejection episode was successfully treated, and by day 61,, the kidney showed minimal signs of injury and continued to function well.
“At two months, the kidney was still functioning fine with no major problems,” said Sykes.
“It suggests that extensive genetic editing of the donor pig organ may not be as important as controlling the response from the patient’s pre-existing T cells in recipients who do not have high levels of antibodies before the transplant,” she added.
Screening confirmed no transmission of pig viruses.
What this means for the future of xenotransplantation
The results challenge the assumption that xenotransplantation needs a long list of genetic changes before an organ can function in a human body. The study also provides a detailed view of how human immunity reacts to a xenograft over time, offering a reference point for future xenotransplantation research. It also shows how rejection can be identified and managed using tools already used in human transplantation.
However, the study only reported on one brain-dead recipient and brain-dead physiology can affect hormones and immune activity, which could shape how the graft behaves. The team also used intensive immune suppression, and this triggered reactivation of human viruses, a risk that needs close attention in living recipients.
The team needs to identify the unknown pig antigens targeted by new antibodies, improve control of pre-existing T cells and assess whether blocking complement earlier in the cascade should be routine. More work and early clinical trials will be needed.
“Additional studies in decedents can help us improve xenotransplants,” said Sykes. “But it is a big sacrifice on the part of the family, and they must ultimately decide when the study stops. The family of the recipient in this study was very generous. What we’ve learned has been invaluable and will help us advance the science of xenotransplantation.”
Reference: Montgomery RA, Stern JM, Fathi F, et al. Physiology and immunology of pig-to-human decedent kidney xenotransplant. Nature. 2025. doi: 10.1038/s41586-025-09847-6
This article is a rework of a press release issued by Columbia University Irving Medical Center. Material has been edited for length and content.
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