A genetically modified pig kidney successfully functioned in a human body for 61 days, establishing a new milestone in xenotransplantation research and bringing scientists closer to addressing the critical organ shortage crisis. The groundbreaking study, conducted by researchers at NYU Langone Health, represents the longest documented case of a pig-to-human kidney transplant.
In July, the research team transplanted the genetically modified pig kidney into Maurice Miller, a 58-year-old man who had experienced brain death due to a brain tumor. The organ was removed on a predetermined date after 61 days of intensive study and monitoring.
Optimal Function Despite Mild Rejection
The transplanted kidney performed "optimally" throughout the study period, according to NYU Langone Health. However, tissue collected during the research revealed some "novel cellular changes" that required additional immunosuppression medication to reverse a mild rejection episode.
"We have learned a great deal throughout these past two months of close observation and analysis, and there is great reason to be hopeful for the future," said Dr. Robert Montgomery, director of the NYU Langone Transplant Institute and chair of the surgery department, who led the research.
The NYU Langone team used a pig kidney with a single genetic modification to "knockout" the alpha-gal biomolecule, which has been identified as a key factor leading to rapid rejection of pig organs by humans. Additionally, the pig's thymus was transplanted alongside the kidney to help protect it from attack by the human immune system.
Parallel Research Confirms Life-Sustaining Function
Supporting these findings, researchers at the University of Alabama at Birmingham Heersink School of Medicine published peer-reviewed research in JAMA Surgery demonstrating that transplanted pig kidneys not only produced urine but provided "life-sustaining kidney function" of filtering waste in brain-dead recipients.
The Alabama team utilized more extensively modified pig kidneys, removing four pig genes that had previously proven barriers to successful cross-species transplantation and inserting six human genes to prevent coagulation and "humanize" the pig kidney. These 10-gene-modified pig kidneys functioned immediately after transplantation and showed no signs of rejection over a seven-day study period.
Critical Evidence for Clinical Translation
The research provides crucial data about how pig kidneys perform in the human environment, addressing a fundamental question that has limited the field's progress.
"Over the last 20 years, we've gained a lot of information about how pig kidneys work to replace the functions in primates. But the critical question – 'Will those data be translated exactly to the human recipients?' – was unknown," said Dr. Adam Griesemer, surgical director of the NYU Langone Pediatric Liver Transplant Program and the Living Donor Transplant Program.
"And for the first time, we're being able to supply that information. So hopefully this also give some assurance to the FDA regarding the safety of initiating phase one clinical trials."
Addressing Organ Shortage Crisis
The research holds particular significance given the scale of the organ shortage crisis. Over 15,000 patients are currently on dialysis and could potentially benefit from kidney transplantation. Xenotransplantation has historically failed due to hyperacute rejection following surgery, even with immunosuppressive drugs.
Both research teams conducted their studies using brain-dead recipients in what is considered pre-clinical human research. The Alabama study confirmed that genetically modified pig kidneys could correct kidney failure and function using standard kidney transplant drugs, with normal creatinine clearance indicating proper waste filtration from blood.
Future Clinical Applications
Researchers emphasize that more work is needed, including studies in living human recipients, to establish whether pig kidney transplants could serve as bridge or destination therapy for people with end-stage kidney disease. However, the progress demonstrated in these studies provides a foundation for advancing toward clinical trials.
The successful function of pig kidneys in human recipients for extended periods, combined with evidence of life-sustaining kidney function, represents a significant step forward in addressing the critical shortage of human donor organs available for transplantation.
