The surgeons who performed the successful transplant have reported that genetically modified pigs kidneys for the first time have provided “life-sustaining” renal function for a full week after the transplantation to a human recipient.
The study’s results show that xenotransplantation, which uses organs genetically modified to prevent rejection from animals as a treatment to alleviate the worldwide shortage of human kidney donors, is a promising therapy. Nearly 5,000 US patients die each year while they wait for a kidney transplant.
Unidentified recipient of pig kidneys, a 52-year old “decedent” who was brain-dead after an accident. After his death, he had asked that his family donate his body to research. The results were published in JAMA Surgery.
Jayme Locke is the leader of the University of Alabama’s transplant team. She said that the [pig] kidneys performed remarkably during the seven-day trial using standard immunotherapy drugs. The surgeons are hoping that the scientific and safety information gained from this study will help them to gain regulatory approval for a human Phase I clinical trial.
The Alabama team performed a similar operation last summer on a man aged 57 who had also been left brain dead by a motorbike crash. The pig kidneys did not reject in the experiment and produced urine, but they were unable to perform a vital renal function – clearing creatinine. This is a waste product that muscles produce. Researchers had to stop the experiment.
In both studies, participants’ own kidneys were removed and replaced by organs taken from pigs that had 10 genetic modifications. These modifications reduce the likelihood of rejection and encourage the organ to grow within the human body. In both studies, four porcine genes were deactivated and added six human genes. The latest study showed that transplanted kidneys from pigs were able filter the blood of creatinine and produce healthy amounts of urine. The renal cells and blood vessel were not damaged in biopsies. Revivicor (a Maryland-based subsidiary of biotechnology company United Therapeutics) developed the animals for xenotransplants. They were then grown in an Alabama facility that was pathogen free.
Roger Lord, a specialist in immunology and transplant biological at Australian Catholic University who was not involved with the study, stated that it “provides significant preliminary evidence that genetically-modified kidneys can function normal following xenotransplantation, and offers hope to people on waiting lists for a kidney transplant”.
Locke said that the study was stopped after 7 days, and the recipient had their life support switched off. However, the evidence showed that the kidneys may have continued to work well for much longer.
She added, “We’ve received permission from the families to extend their studies to 30 days if they feel it is necessary.”
Since the 1960s, xenotransplants are a major focus of medical research. Genetics and immunology advances have only just recently enabled regulators to consider the use of this technology in clinical practice.
The first man who received a pig heart transplant at the University of Maryland Medical Center died just two months later. A autopsy revealed that the new heart did not show any signs of rejection, but he died from “heart failure due to complex factors”.
Locke thinks that the US regulator Food and Drug Administration should allow a Phase I clinical trial of kidney transplants in living recipients to start as soon as it is possible, without insisting further data from monkey studies.
She said, “I don’t think that the non-human primates model will ever provide us with the answers for FDA applications.” “I was hoping that the FDA would approve Phase 1 trials this year, but I now don’t believe that will happen.”