Surgeons Improve Function of Kidneys Transplanted From Genetically Altered Pigs

The News

Surgeons in Birmingham and New York City on Wednesday reported advances in the transplantation of organs obtained from pigs that have been genetically modified to prevent rejection after they are implanted in humans.

Researchers at the University of Alabama at Birmingham published a peer-reviewed study showing that modified pig kidneys performed complex life-sustaining functions in a brain-dead patient for a full week.

In an apparent response, surgeons at New York University announced that a kidney from a genetically modified pig continued to function well after 32 days in a brain-dead patient maintained on a ventilator, the longest period for such an experiment.

The patient has shown no signs of rejecting the organ, said Dr. Robert Montgomery, director of the NYU Langone Transplant Institute. The research has not yet been published in a journal.

Why It Matters: An inadequate supply of donor organs.

The research is part of a radical scientific effort to develop an alternative source of transplant organs for Americans whose kidneys, hearts and other organs have failed.

The greatest need is for kidneys. More than 800,000 American have kidney failure, and over 100,000 are on a waiting list for a transplant. Kidney dialysis can keep patients alive, but the gold standard treatment is an organ transplant.

Yet fewer than 25,000 kidney transplants are performed each year because of a scarcity of human donor organs. Thousands of people on the waiting list die each year.

“A lot of folks think dialysis is an appropriate alternative, but people die on dialysis,” said Dr. Jayme Locke, director of U.A.B.’s Comprehensive Transplant Institute and a lead author of the new report.

A number of studies last year demonstrated that pig kidneys that had been transplanted into brain-dead individuals made urine, an essential function, for short periods of time. But the U.A.B. study is the first to clearly show that the organs also filter creatinine, a byproduct of muscle contractions that must be removed from the blood.

“The really new finding here is that these pig kidneys can clear enough creatinine to support an adult human,” Dr. Locke said. The U.A.B. paper was published Wednesday as a research letter in JAMA Surgery.

The kidney performs numerous functions, among them balancing the body’s fluids, regulating blood pressure and controlling pH levels. “If you want to have life-sustaining kidney function, the kidneys have to do more than just make urine,” Dr. Locke said.

Background: Animal organs may be a solution to the shortage.

Xenotransplantation, the transplantation of animal organs into humans, has long been a goal of surgeons. Recent advances in cloning and genetic engineering have led to rapid breakthroughs.

In 2021, surgeons at NYU Langone Health announced they had attached a kidney from a genetically modified pig to a brain-dead individual who was maintained on a ventilator. A few months later, researchers at the University of Maryland transplanted a heart from a genetically modified pig into a 57-year-old patient with heart failure. He died two months later, and traces of a virus known to infect pigs were found in the organ.

Dr. Locke and her colleagues reported last year that they had for the first time successfully transplanted kidneys from a genetically modified pig into the abdomen of a brain-dead man.

The organs used in the experiments at U.A.B. and N.Y.U. are slightly different, though both were derived from pigs provided by Revivicor, a subsidiary of United Therapeutics Corporation, a biotech company.

The kidneys used at U.A.B. came from pigs that had undergone 10 gene modifications, while the kidneys used at N.Y.U. had only one genetic modification. The N.Y.U. procedure also calls for embedding the pig’s thymus gland, which is responsible for educating the immune system, underneath the outer layer of the new kidney to prevent an immune-system attack.

What’s Next: A clinical trial in humans.

So far, transplants of genetically modified pig kidneys have been made only to brain-dead patients. Dr. Locke and her colleagues are in discussions with the Food and Drug Administration about launching a first clinical trial in live patients.