Breaking Ground in Transplantation: A New Era with Xenotransplantation

On March 16th, 2024, Richard Slayman made history at Massachusetts General Hospital as the first person to receive a genetically modified pig kidney transplant. Sadly, Mr. Slayman passed away two months later, but his contribution to the field of xenotransplantation will never be forgotten. 

“Patients are at the forefront of everything we do here at the National Kidney Foundation (NKF). We dream of a day when no one dies waiting for a kidney transplantation. To that end, we thank Mr. Slayman for his bravery and express our deepest sympathies to his family,” said Kevin Longino, NKF’s CEO. “Mr. Slayman’s compassion and selflessness have given hope for a brighter future with more transplant opportunities. His legacy will be measured in the lives he’s helped save."

With more than 25 years of xenotransplantation involvement, NKF recognizes this is an important step forward. Still, we know there is work to do before xenotransplants could potentially become a mainstream treatment for the nearly 90,000 people on the kidney transplant waitlist. NKF will be there every step of the way, collaborating with professionals, advocating for safe, innovative treatments, and ensuring the patient's perspective is front and center. By working together, we can create a future where everyone who needs a kidney gets one–a future where there are Transplants for All.

Xenotransplantation (pronounced zee-no-tran-splan-TAY-shin) is the experimental process of transplanting organs across species. In this case, transplanting a genetically modified pig kidney into a human recipient. 

There are currently no clinical trials for pig kidney xenotransplantation. The historic transplant was approved through the FDA's expanded access pathways or compassionate use. Expanded access allows people with life-threatening conditions to receive experimental treatments if no other option exists.

So, what is holding things up? Before human clinical trials can begin, the FDA and researchers have to think through several practical and ethical issues.

Some Xenotransplant Hurdles Include:

• Rejection: All transplant recipients take medication to prevent their bodies from rejecting the new organ. The risk of rejection with animal organs is much higher because our DNA is different. Minor changes to the animal's DNA help lower the risk.
• Infection: There may be a risk of infection from animal-specific diseases spreading among humans. Early recipients and the people they are close with may have to be monitored to ensure this doesn't happen.
• Function: Early evidence shows that pig kidneys can perform basic kidney functions, like cleaning toxins. We don’t know if they will perform the kidneys’ other roles, like helping regulate blood pressure.

More people need organs than what is available. Xenotransplantation may help us bridge that gap—but where does the process currently stand? Sign up for NKF Live: Xenotransplantation on June 25th, 2024 to get your questions answered by the experts. 

Xenotransplantation using pig organs is not new; humans have explored the idea for centuries.One of the first recorded instances dates back to 1838. A doctor transplanted a pig cornea into a human to fix their eyesight.¹ Unsurprisingly, this early attempt did not work.

Significant strides were made only after scientific advancements in dialysis, immunosuppressant drugs, and gene editing.

Timeline of Xenotransplantation Milestones in the U.S.

• 1960s: Immunosuppressive drugs are identified. Xenotransplant research became popular because healthcare practitioners believe the drugs will stop the xenotransplanted organ from rejecting. Attempts were made using nonhuman primate organs in humans. All were unsuccessful.
• 1990s: Pigs become the ideal choice for xenotransplantation because they are more widely available than nonhuman primates, and their organs are similar to humans.²
• 1999: NKF surveys the nation to understand what people think about xenotransplantation. Over 71% of people surveyed confirmed they would consider xenotransplantation for a loved one if a human kidney was not available. 
• 2019: A macaque survives more than one year with a life-supporting kidney xenotransplanted from a genetically altered pig.³
• September 2021: The University of Alabama successfully transplants a genetically modified pig kidney into a brain-dead human. 
• September and November 2021: NYU Langone Health successfully transplants a genetically modified pig kidney into two brain-dead humans. 
• January 2022: The University of Maryland School of Medicine transplants a genetically modified pig heart into a living recipient. The recipient passes away two months later. It is not known if the transplant played a part in the death. 
• June and July 2022: NYU Langone Health transplants two genetically engineered pig hearts into recently deceased humans to safely gather data on and improve their current xenotransplantation practices.
• April 2022: NKF holds the First Scientific Workshop on Xenotransplantation to better understand how recent work in the xenotransplant field will inform future clinical trials. 
• November 2023: NKF hosts a patient-focused meeting with the FDA to collect the patient perspective of xenotransplantation. This feedback was shared with Massachusetts General Hospital, which completed the first xenotransplant of a pig kidney in a living human.
• March 2024: Massachusetts General Hospital successfully transplants a genetically edited pig kidney into a living adult with end-stage kidney disease. The recipient, Mr. Slayman, passes away in May 2024. It is not believed that the transplant played a part in the death.
• April 2024: NYU Langone Health successfully performs the first-ever combined heart pump and pig kidney transplant. He receives NKF’s Prestigious Excellence in Transplantation Award for his contributions to the field of transplantation. 

Listen to our podcast episode on xenotransplantation with Dr. Jayme Locke, the lead doctor and surgeon behind the first successful xenotransplantation of a pig kidney into a brain-dead human, to learn more.

As experts work to ensure xenotransplantation is a safe treatment option, NKF will continue supporting research and putting patients front and center. This includes sharing the discoveries from our externally led patient focus group with the FDA and companies preparing for clinical trial applications.

If the FDA approves the clinical trials, xenotransplantation will go through four phases:

• Phase 1: Determine safety and identify side effects of the procedure.
• Phase 2: Measure effectiveness and further study the procedure's safety.
• Phase 3: Confirm effectiveness, monitor side effects, and compare with standard or similar treatments.
• Phase 4: Continue to study the recipients in the general population further to understand the treatment's benefits and optimal use. This phase comes after the FDA approves the treatment. 

Until then, pre-clinical trial studies, compassionate use cases, and patient feedback provided by NKF will continue shaping the future of xenotransplantation. 

Learn more about clinical trials. 

Do you want to help shape the future of kidney research? Join NKF's Kidney Research Connect to share what research outcomes are important to you.

Sources

¹Cooper DK. A brief history of cross-species organ transplantation. Proc (Bayl Univ Med Cent). 2012 Jan;25(1):49-57. doi: 10.1080/08998280.2012.11928783. PMID: 22275786; PMCID: PMC3246856.

²Groth CG. The potential advantages of transplanting organs from pig to man: A transplant Surgeon's view. Indian J Urol. 2007 Jul;23(3):305-9. doi: 10.4103/0970-1591.33729. PMID: 19718335; PMCID: PMC2721611.

³Kim SC, Mathews DV, Breeden CP, Higginbotham LB, Ladowski J, Martens G, Stephenson A, Farris AB, Strobert EA, Jenkins J, Walters EM, Larsen CP, Tector M, Tector AJ, Adams AB. Long-term survival of pig-to-rhesus macaque renal xenografts is dependent on CD4 T cell depletion. Am J Transplant. 2019 Aug;19(8):2174-2185. doi: 10.1111/ajt.15329. Epub 2019 Apr 5. PMID: 30821922; PMCID: PMC6658347.