The two transplant surgeries provide hope of someday closing the enormous gap between the supply of kidneys and demand for them by showing that pig kidneys can sustain normal human function for an extended period of time. Until the new results were released Wednesday, that had not been demonstrated, according to the surgeons involved and other experts.
“This is the first time in history that anyone has been able to show a genetically modified pig kidney is able to maintain life-sustaining kidney function,” said Jayme E. Locke, lead author of the JAMA Surgery research.
The long waiting list for kidneys
On Wednesday, 103,479 people were on the waiting list for transplant organs in the United States, with 88,651 seeking kidneys, according to data kept by the United Network for Organ Sharing (UNOS). In 2022, 26,000 people received kidney transplants, according to NYU Langone Health.
Many people die after waiting years for a kidney, and others become too sick to receive a transplant. Some never make the waiting list. About 808,000 Americans are living with end-stage kidney disease, 69 percent of them on dialysis and the rest with transplants, according to the National Institute of Diabetes and Digestive and Kidney Diseases.
Kidneys, like livers, can be procured from deceased and living donors, who must be matched with recipients on various measures of suitability.
The critical advances reported Wednesday were the transplanted pig kidneys’ ability to concentrate urine and clear creatinine, a byproduct of muscle function that is toxic if it builds up in the human body, Locke said. She said the University of Alabama at Birmingham experiment could have gone on longer but was ended in deference to the decedent’s family.
Robert Montgomery, who led the NYU Langone procedure and is director of the NYU Langone Transplant Institute, said researchers “are at a point now where we have quite a large array of information from nonhuman primates.” How “translatable” that information is to humans is what the research is showing for the first time, he said.
David Klassen, chief medical officer for UNOS, agreed, saying that “this is a critical step towards clinical trials in living patients because it may provide evidence of longer term normal physiological function without rejection.”
One genetic alteration
In the NYU Langone transplant, the specially bred pig from which the kidney was procured required just one genetic alteration, to remove a protein that human immune systems attack shortly after surgery. Surgeons also implanted the pig’s thymus gland, which helps train the immune system, by sewing it under the outer layer of the kidney, and used immunosuppressive drugs to prevent rejection later on.
Managing the condition of the brain-dead man, who on Wednesday still had a heartbeat and was breathing with the aid of a ventilator, for an extended period also requires extensive efforts by critical care personnel. But the work has revealed information about longer-term use of animal organs, the doctors said.
The researchers expect to follow the patient for another month.
The man whose body underwent the kidney transplant at NYU was identified as 57-year-old Maurice “Mo” Miller, who died of a brain tumor. His sister spoke at Wednesday morning’s news conference, saying her brother would have valued the contribution he was able to make to the science of transplantation.
It was only two years ago that Montgomery transplanted the first pig kidneys into human decedents. Separately, in January 2022, University of Maryland surgeons implanted a genetically modified pig’s heart in a critically ill man, who died two months later. The donor heart was found to be infected with a porcine virus.
The NYU Langone surgeons said they used a more sensitive test in the hope of screening out such viruses before the transplant.
‘A lifesaving therapy’
With the results released Wednesday, both Montgomery and Locke said they can envision moving toward the early stage of clinical trials to identify the safety of transplanting pig kidneys into live humans.
“This is clearly a lifesaving therapy,” she said.
The genetic alteration in the NYU Langone study knocked out a carbohydrate molecule known as Alpha-gal, for short. Humans do not produce the substance and create high levels of antibodies against it, which has in the past proved a formidable obstacle to xenotransplantation.
“Now that it can be completely removed from the pig, that allows us to move forward,” Montgomery said.
Still, the team said, pigs have 1,000 proteins that humans don’t, and it can take 10 to 14 days to see how a person’s immune system reacts to them. Getting beyond that stage with this patient at NYU Langone is a first sign that long-term viability of the organ and patient is possible, they said.
SOURCE: Washington Post