Woman receives genetically modified pig kidney transplant after heart pump surgery

Woman becomes first person to receive both pig kidney transplant and heart pump

Written by Tanya Lewis

People with heart failure may be eligible for a heart transplant. People with kidney failure may be lucky enough to receive a kidney transplant. However, for many people with symptoms such as: both If you have heart or kidney disease and are not eligible for a transplant or cannot receive both organs in time, your options are very limited.

But scientists at NYU Langone Health in New York City are conducting a first-of-its-kind surgery that involves installing a left ventricular assist device (LVAD), or mechanical heart pump, followed by implantation in genetically modified pigs. completed. kidney. This is the first time an LVAD patient has received any type of transplant (other than a heart transplant to replace the device) and the second time a genetically modified pig kidney has been transplanted into a living person. .

This achievement creates a potential avenue to treat people with both heart and kidney disease. “Our success with this one patient will open up many possibilities for thousands of patients with heart and kidney problems,” said Dr. One Nader Moazami said: Mechanical circulatory support at New York University Grossman School of Medicine, where LVAD surgery was performed.

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There is a huge demand for kidney and other transplants, but there is a near scarcity of available donor organs. But in recent years, scientists have made great strides in transplanting organs from non-human species to humans, known as xenotransplantation.

In late March, surgeons at Massachusetts General Hospital announced they were the first living person to complete a genetically engineered pig kidney transplant, on a 62-year-old man with end-stage renal disease named Richard Suleiman. According to the transplant team, Suleiman suffered an initial immune rejection reaction, but was successfully treated, was discharged from the hospital, and is now living at home and doing well.

The latest recipient of LVAD surgery and kidney xenotransplantation was Lisa Pisano, a 54-year-old New Jersey grandmother who had heart failure and end-stage renal disease and was on dialysis. Ms. Pisano had a number of contraindications that made it possible for her to both have her organs found and survive after surgery, and her life expectancy was very limited, making her eligible for a human heart and kidney transplant. There was no. Her experimental surgery was performed under the U.S. Food and Drug Administration's Expanded Access Program (also known as “compassionate use”), a pathway for people with serious illnesses who have few treatment options.

First, Moazami and his team implanted the LVAD in Pisano on April 4th. Most people on dialysis are not eligible for an LVAD because the mortality rate is very high. This is where xenotransplanted kidneys come into play.

On April 12, a team led by Robert Montgomery, chief of surgery and director of New York University's Langone Transplant Institute, transplanted a kidney containing a pig thymus gland into Pisano. The pigs had been gene-edited to remove a gene that causes the production of a sugar called alpha-gal, which can trigger an immune response in the human body and cause it to reject the pig's organs. The thymus was included in the hope that training the immune system not to attack the foreign kidney would ultimately reduce the amount of immunosuppressive drugs needed after transplantation.

The research team needed to find the right flow rate for the heart pump so that the transplanted kidney could function effectively. But as soon as they did that, the organs started producing urine and creatinine, important waste products that the kidneys were supposed to remove. “There were things we had to learn because it had never been done before,” Montgomery says.

There were several important differences between the NYU Langone xenotransplant and the previous xenotransplant at Massachusetts General. “He basically has two potential schools of thought about how xenotransplants can help patients,” said the head of transplantation at Massachusetts General, who led the team that performed the previous pig kidney transplant. Leonardo Riera, head of kidney transplant medicine, said: Meanwhile, kidney transplant candidates on the waiting list, who unfortunately do not have a donor, have been approved to receive a human kidney transplant, he says. Such was the case with Suleiman, his team's xenograft patient. Another way in which xenotransplantation can be helpful is that “people who are not candidates for human organ transplantation but [who is offered] As in Pisano's case, xenotransplantation may be considered as a last resort.

Riera says Pisano was probably much sicker than Suleiman. Unlike Suleiman, she was not a candidate for human organ transplants and suffered from both heart and kidney failure, while Suleiman only suffered from kidney failure. “Both have values.” [types of surgery]” says Riera. However, “doing that to a patient who is not a patient is [human organ] Transplant candidates are usually at higher risk. ”

Additionally, Pisano received organs from pigs that had undergone only one genetic modification, while Suleiman received organs from animals that had undergone 69 genetic modifications. It is not yet known whether such additional editing is required for long-term survival of such xenotransplanted organs in humans.

So far, Pisano has shown no signs of acute immune rejection. But that tipping point may come about a month after surgery, Montgomery said. For now, he and his colleagues continue to keep a close eye on her.

“It's incredibly exciting to have a second gene-edited pig kidney transplanted into a living human,” said Jamie Locke, director of transplantation and director of transplant surgery at the University of Alabama at Birmingham. I think so,” he says. They had previously performed pig kidney transplants on humans who had experienced brain death. “As with any transplant, we want to make sure we have the immune system under control in the early stages and make sure there is no early rejection,” she says. “If this works, it's an incredibly positive thing.”

Two recent kidney xenotransplants will provide scientists with valuable knowledge about the safety and effectiveness of this procedure. But the New York University Langone and Mass General University teams believe they need to target more people before xenotransplantation becomes an approved treatment and can help address the huge demand for organs. It points out that clinical trials are an important next step.

As for Pisano, Montgomery said she was aware of the risks of the surgery but felt it was worth it given the chance to extend her life. “She knew she was going to die and that she didn't have much time,” he says. “From the beginning she said, 'I want to spend some time with her grandchildren, I want some more time.'”