Kidney Transplanted from a Pig Lasts 32 Days in Human Recipient

Xenotransplantation of Pig Kidneys Performs Well After 32 Days in Humans

Highlights:

Surgeons at NYU Langone Health have successfully transplanted a genetically engineered pig kidney into a deceased individual
It demonstrated sustained functionality for 32 days without rejection
This accomplishment represents a crucial step toward addressing the organ shortage crisis

Can we envision a future where the shortage of organ donors is no longer a barrier to saving lives?

Surgeons from NYU Langone Health have successfully transplanted a genetically modified pig kidney into a deceased individual who met neurological criteria for death. This kidney has remained functional for a remarkable 32 days within the recipient, whose heart was kept beating via ventilator support.

This achievement marks the longest duration that a gene-edited pig kidney has maintained functionality within a human body. This milestone not only offers hope for an alternative, sustainable supply of organs for transplantation but also represents a significant step forward in xenotransplantation research ().

Test Your Knowledge on Kidney Transplantation
Kidney transplantation is a surgical procedure done to remove a diseased kidney and replace it with a healthy one from a donor. A person requires one healthy functioning kidney to keep the body functions normal ( ). Once a ...

‘The transplanted pig kidney remained functional and sustained the recipient's kidney function for 32 days without encountering signs of rejection. #KidneyTransplant #Pig #Human’

Pig Kidney in Human: A Case of Xenotransplantation

The groundbreaking procedure took place on July 14, 2023, under the leadership of Dr. Robert Montgomery, MD, DPhil. Dr. Montgomery holds the position of H. Leon Pachter, MD, Professor of Surgery, chair of the Department of Surgery, and director of the NYU Langone Transplant Institute. This endeavor marked the fifth instance of xenotransplantation at NYU Langone. The monitoring of the patient's condition is ongoing, and the study will extend until mid-September 2023.

According to Dr. Montgomery, "This work showcases the ability of a pig kidney, modified with just a single genetic alteration and without experimental drugs or devices, to effectively replace the function of a human kidney for over 32 days without encountering rejection." Dr. Montgomery, who had previously conducted the world's first gene-edited pig kidney transplant into a deceased human on September 25, 2021, followed by a second similar procedure on November 22, 2021, further explained that surgeons from the Transplant Institute also accomplished two gene-engineered pig heart transplants during the summer of 2022.

Kidney Transplantation
Since the early times, the novel idea of transplanting tissues and other body parts from one organism to the other has captured the imagination of successive generations.

Kidney Transplant: Overcoming Rejection Challenges

The main obstacle in xenotransplantation involves averting hyperacute rejection, a phenomenon that usually manifests minutes after connecting an animal organ to the human circulatory system. By genetically modifying pigs to disable the gene responsible for alpha-gal, a biomolecule linked to rapid antibody-mediated rejection of pig organs by humans, NYU Langone successfully prevented immediate rejection in all five xenotransplants.

Additionally, the pig's thymus gland, responsible for educating the immune system, was embedded beneath the kidney's outer layer to prevent delayed immune responses. The combination of these modifications has proven effective in preventing organ rejection while sustaining kidney function.

To ensure that the pig kidney was solely responsible for maintaining kidney function, both of the recipient's original kidneys were surgically removed. Subsequently, a pig kidney was transplanted, which immediately began producing urine without encountering signs of hyperacute rejection.

Throughout the observation period, intensive care clinical staff ensured the decedent's support, while the pig kidney's performance was closely monitored through weekly biopsies. The levels of creatinine, a waste product indicative of kidney function, remained within the optimal range throughout the study, with no biopsy evidence of rejection.

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Ethical and Regulatory Approvals for the Transplantation

The surgery is part of a broader study approved by a dedicated research ethics oversight board at NYU Langone, conducted in consultation with the New York State Department of Health. This crucial research, poised to save numerous lives in the future, was made possible through the generosity of a 57-year-old male donor's family. The donor had chosen to donate his body after being declared brain dead, and his organs or tissues were deemed unsuitable for standard transplant procedures.

The nonprofit organization LiveOnNY, responsible for facilitating organ and tissue donations in the greater New York City area, played a pivotal role in informing, supporting, and collaborating with the donor family during the authorization process.

A Significant Leap Towards Organ Availability

In the United States, more than 103,000 individuals are awaiting transplants, with nearly 88,000 of them needing kidneys, as per recent data from the federal Organ Procurement and Transplantation Network (OPTN). In 2022, approximately 26,000 people received kidney transplants. Meanwhile, almost 808,000 individuals in the United States suffer from end-stage kidney disease.

Dr. Montgomery expressed, "The shortage of available organs is causing needless loss of life, and I firmly believe that xenotransplantation offers a viable solution."

The kidney and thymus gland utilized in the procedure were sourced from a GalSafe pig, genetically engineered by Revivicor Inc., a subsidiary of United Therapeutics Corporation. In December 2020, the U.S. Food and Drug Administration (FDA) granted approval for the GalSafe pig as a potential source of human therapeutics, as well as a food source for individuals with alpha-gal syndrome, a meat allergy stemming from tick bites.

While earlier gene-edited pig organ transplants involved up to 10 genetic alterations, this recent study demonstrates that a single-gene knockout pig kidney can function optimally for at least 32 days without experiencing rejection.

Dr. Montgomery commented, "Our findings suggest that in kidneys, eliminating the gene responsible for hyperacute rejection, in combination with established immunosuppressive medications, can manage transplantation successfully in humans for an extended period—potentially even long-term."

To ensure safety, the NYU Langone team employed standard transplant immunosuppression medications and conducted a thorough screening of porcine cytomegalovirus (pCMV) in the donor pig. Recent research indicates that pCMV might impact organ performance and trigger organ failure. However, no pCMV was detected during the 32-day period, and meticulous monitoring was carried out for porcine endogenous retrovirus (PERV) and other viruses.

To conclude, The recipient of the pig kidney will continue to be monitored for an additional month, with consent from the family, approval from the ethics committee, and ongoing support from United Therapeutics. The forthcoming weeks' data will be analyzed to deepen the understanding of this remarkable medical advancement.

Dr. Montgomery stated, "We believe that by using an FDA-approved pig in combination with our existing xenotransplantation research, we are moving closer to the clinical trial phase. While we recognize the potential to save countless lives, safety, and care remain our top priorities as we progress."

Reference:

Pig Kidney Xenotransplantation Performing Optimally After 32 Days in Human Body - (https://nyulangone.org/news/pig-kidney-xenotransplantation-performing-optimally-after-32-days-human-body)

Source-Medindia