Redefining Transplant Possibilities: The Emergence of Kidney Xenotransplants

In the United States, there are more than 100,000 people on the national organ transplant waitlist. Of these, nearly 90,000 are seeking a kidney transplant, and 11 people die every day waiting for a new kidney they never receive.1,2

The number of people seeking a life-saving kidney transplant far exceeds the number of kidneys available for transplant. However, renewed interest and recent progress in the transplantation of solid organs across species, known as xenotransplantation, may have the potential to reshape the narrative around kidney transplantation.

A Long Road to 2025: Decades of Xenotransplant Research

Although enthusiasm around renal xenotransplantation surged in 2025, its history stretches back more than half a century. Kidney xenotransplant research became popular in the 1960s, when investigators explored nonhuman primates as potential kidney donors, but with poor clinical results. Pigs later emerged as the preferred source in the 1990s, largely due to anatomical compatibility, availability, and the feasibility of large-scale gene editing.3,4

Following decades of research, in 2021, several successful transplants of genetically modified pig kidneys into brain-dead humans took place at the University of Alabama and NYU Langone Health.4

“I think what really broke the ice was when we started to put these organs into decedents, brain dead individuals, and were able to follow them for 1 or 2 months and provide that additional level of reassurance that there wasn't transmission of pathogens of concern or of interest,” Robert Montgomery, MD, PhD, chair of the Department of Surgery and director of the NYU Langone Transplant Institute, explained to HCPLive, describing how this knowledge helped pave the way for later compassionate use instances of kidney xenotransplantation.

Indeed, a few years later, in 2024, Massachusetts General Hospital made history when it successfully transplanted a genetically edited pig kidney into a living adult with end-stage kidney disease (ESKD), though it only lasted for 2 months before the recipient passed away.4

“Xenotransplantation is perhaps the most exciting frontier in kidney transplant that we've seen,” Pranav Garimella, chief medical officer of the American Kidney Fund, told HCPLive. “It's not new. It's been around for a long time, but this is the first time we've seen substantial improvements in patient outcomes and substantial longevity in these xenotransplanted kidneys.”

Major Advances in 2025

Momentum accelerated further in early 2025 when Massachusetts General Hospital successfully completed its second transplant of a genetically-edited pig kidney into a living recipient in January. The procedure was performed under the US Food and Drug Administration (FDA) Expanded Access Protocol (EAP), a pathway allowing patients with serious, life-threatening illnesses or conditions to access experimental treatments when no comparable options are available, and used a kidney with 69 genomic edits provided by eGenesis.5

The 66-year old male patient who received the xenotransplant had been on dialysis for more than 2 years due to end-stage kidney disease (EKSD). Beyond the daily struggles of dialysis, his path to a kidney transplant was further complicated by his O-group blood type, which can significantly extend wait time for a kidney transplant.5

Just a few weeks later, the FDA made history when it cleared the first-ever clinical trials of xenokidneys with United Therapeutics’ investigational UKidney™ derived from a 10 gene-edited source pig and eGenesis’ 69 gene-edited pig kidney. Intended to support a Biologics License Application with the Agency, United Therapeutics’ clinical study was designed to enroll an initial cohort of 6 patients with ESKD and expand to up to 50 participants who have been assessed and determined to be ineligible for a conventional allogeneic kidney transplant for medical reasons or who have been on the kidney transplant waitlist but are more likely to die or go untransplanted than receive a deceased donor kidney transplant within 5 years.6,7

“I've been in the field for decades, and I remember when I started as a young surgeon in transplantation, xenotransplantation was a field that you pursued in the lab using small animals, and the barriers seemed insurmountable,” Richard Knight, MD, medical director of transplant diagnostics at Thermo Fisher Scientific, told HCPLive. “Lots of good researchers gave up, but this year, the progress has been amazing.”

How Close Are We to a Clinical Solution?

Despite these advances, experts emphasize that xenotransplantation is far from ready for routine practice. Encouragingly, Montgomery notes that early pig kidney xenografts have “worked right out of the box” rather than failing from accelerated rejection, a problem that has plagued early primate studies.

Still, immunological concerns exist regarding the spread of infection from animal-specific diseases among humans. An unmet need exists for an immunosuppressive regimen capable of preventing rejection but not inducing infection in xenotransplanted patients.4

“The xenograft barrier is enormous, although they've made tremendous progress in that,” Knight told HCPLive. “The second big concern is transmission of viruses, pig viruses, to humans, which can be controlled through careful selection and breeding of these pigs and potentially the downregulation of these viruses.”

“Let's face it, this is very complicated stuff,” Montgomery added. “It's not out of the gates. Nothing like this out of the gates is in its final form. The gene edits, the immunosuppression, it's going to get better as time goes on.”

In addition to safety, the long-term efficacy of these organs remains to be fully proven. On average, a kidney transplant from a living donor lasts about 15 to 20 years, and a kidney from a deceased donor lasts about 8 to 12 years. Current kidney xenotransplant data only demonstrates the viability of these organs through a few months.8

Because of this, Garimella says he still only sees xenotransplantation as a bridge to transplantation with a human kidney: “Whether or not these kidneys will last the 5, 10, 15, 20, years that we are seeing human kidneys last now is unknown.”

He and Montgomery both draw parallels to what left ventricular assist device (LVAD) serves as for heart transplantation, predicting that xenotransplantation may end up playing a similar role in the context of kidney transplantation.

“We might see that maybe in some cases, it's going to be a bridge to a transplant, and in other cases, it depends from organ to organ and how it evolves, but it could be something that's going to last long enough that it'll be destination therapy,” Montgomery explained.

Ethical and Practical Considerations

Should xenotransplantation make it to frontline use as a potential solution to the current organ donor shortage, Garimella says large-scale implementation will require addressing ethical, regulatory, and logistical challenges.

Knight additionally questions whether or not xenotransplant can be scaled up, noting hundreds or thousands of these transplants would need to be done each year, as well as cost concerns.

“We can come up with all sorts of great medical advances. But the fact of the matter is, if these advances are too expensive, they're going to go nowhere,” he said. “I'm very interested in finding out more about whether this is scalable and if we can do it in a way that’s economically feasible.”

Looking Ahead

The progress of 2025 represents a turning point, not the finish line, but many in the field are optimistic that xenotransplantation may finally offer a viable pathway for thousands of patients who otherwise have no options.

“Beyond living donor and deceased donation, the only other option is xenotransplantation, and that's what I think clinicians are most excited about, that this may be a viable path to get more patients transplanted who simply don't have other options,” Knight said.

References

1. Health Resources & Services Administration. Organ Donation Statistics. May 2025. Accessed December 11, 2025. https://www.organdonor.gov/learn/organ-donation-statistics

2. UNOS. 90,000 people are waiting for a kidney. Here's one way to get them a kidney faster. January 27, 2025. Accessed December 11, 2025. https://unos.org/news/90000-people-are-waiting-for-a-kidney-heres-one-way-to-get-them-a-kidney-faster/

3. Cooper DKC, Ekser B, Tector AJ. A brief history of clinical xenotransplantation. Int J Surg. 2015;23(Pt B):205-210. doi:10.1016/j.ijsu.2015.06.060

4. National Kidney Foundation. Breaking Ground in Transplantation: A New Era with Xenotransplantation. May 31, 2024. Accessed December 11, 2025. https://www.kidney.org/news-stories/breaking-ground-transplantation-new-era-xenotransplantation

5. Brooks A. Second Xenotransplant with Gene-Edited Pig Kidney Performed at Mass General. HCPLive. February 7, 2025. Accessed December 11, 2025. https://www.hcplive.com/view/mass-general-performs-second-xenotransplant-gene-edited-pig-kidney

6. Brooks A. FDA Clears First Xenotransplant Trial for Gene-Edited Kidneys. HCPLive. February 3, 2025. Accessed December 11, 2025. https://www.hcplive.com/view/fda-clears-first-xenotransplant-trial-gene-edited-kidneys

7. Deeley M. FDA greenlights first clinical trials for genetically modified pig kidney transplants in humans. American Kidney Fund. February 6, 2025. Accessed December 11, 2025. https://www.kidneyfund.org/article/fda-greenlights-first-clinical-trials-genetically-modified-pig-kidney-transplants-humans

8. National Kidney Fund. Kidney Transplant. March 15, 2024. Accessed December 11, 2025. https://www.kidney.org/kidney-topics/kidney-transplant