Kidney transplants: Gene-edited pig organs are not rejected by brain-dead person

In an experiment paving the way for clinical trials, two pig kidneys produced urine for 77 hours after transplantation into the body of a brain-dead man

By Michael Le Page

Two pig kidneys genetically engineered to prevent rejection by the immune system have been transplanted into a brain-dead man in the US as a first step towards treating patients. The kidneys were not rejected during the 77 hours that the experiment lasted.

“This game-changing moment [is] a major milestone in the field of xenotransplantation, which is arguably the best solution to the organ shortage crisis,” surgeon Jayme Locke at the University of Alabama at Birmingham said in a statement. “We have… obtained the safety and feasibility data necessary to begin a clinical trial.”

The experiment took place several months ago but was published in the American Journal of Transplantation today. The kidneys came from the same line of genetically modified pigs as the heart transplanted into 57-year-old David Bennett on 7 January. While Bennett got the pig heart because there were no other options for him, the kidney transplant was done as an initial safety test only.

The recipient, Jim Parsons, also 57, was a registered organ donor but none of his organs were suitable for transplantation. His family gave permission for his body to kept alive on a ventilator so the study could be done. His own kidneys were removed and replaced with the genetically engineered pig kidneys.

“Jim would have wanted to save as many people as he could with his death, and if he knew he could potentially save thousands and thousands of people by doing this, he would have had no hesitation,” his ex-wife Julie O’Hara said in a statement.

Pig organs cannot normally be transplanted into people because they are rejected by the human immune system, even if people are given immunosuppressant drugs. But the pigs created by US firm Revivicor have been genetically modified to prevent rejection.

Four genes have been switched off, including some that code for the proteins that provoke the immune response in humans. The pigs also have six added human genes.

The pig kidneys were not rejected during the 77-hour experiment. They produced urine but did not remove a substance called creatinine from the blood, a key measure of normal kidney function. The team are not sure why this was the case, but it could be related to Parsons’ condition.

One potential issue is that pigs have a lower blood pressure than people, meaning the blood vessels in pig kidneys might be damaged by the higher blood pressure after transplantation. But the team saw no sign of any problems.

Another concern is that viruses lurking in the genomes of pigs might be able to infect people, but the team found no sign of this. At least one other company working on creating pigs suitable for transplants, however, is deleting all the viral genes to ensure this cannot happen.

Journal reference: American Journal of Transplantation, DOI: 10.1111/ajt.16930