B.C. organ donor project aims to reduce kidney rejection with better matches

Researchers in British Columbia have set their sights on virtually eliminating organ rejection by using advanced genetic testing to better match patients with kidney donors.

Dr. Paul Keown, lead researcher for the pilot project and a University of British Columbia specialist in immunology and transplantation, said the new technology involves genetic sequencing at the molecular level to significantly reduce the risk of a recipient’s immune system rejecting a donor kidney.

“We hope to see rejection almost disappear,” he said of the project, partly funded by Genome British Columbia and Genome Canada through a partnership with Canadian Blood Services.

About half of all transplants fail over time due to rejection, Keown said.

Currently, patients awaiting a transplant are tested for the same blood type with a potential donor. They are also tested to determine if they have antibodies — from pregnancy, a blood transfusion or a previous transplant — that would cause their immune system to attack a donor kidney.

It’s long been known that the immune system uses a set of molecules called HLA, or human leukocyte antigens, to distinguish between its own cells and those from a donor organ, leading to possible rejection. But matching donors and recipients is difficult because there are more than 30,000 variations of HLA molecules.

Dr. James Lan, a transplant nephrologist who is involved with the project, said the new method compares small sequences called epitopes, the specific parts of HLA that are recognized by the immune system. There are only about 150 epitopes so it would be easier to match recipients and donors, he added.

One in three transplants fails over a decade, mainly due to rejection in half the cases, but it’s possible for someone to live with a well-matched kidney for about 30 years, said Lan, medical director of the Immunology Laboratory at Vancouver General Hospital.

The new genetic sequencing technology can help find a match within about six hours, Lan said. It also allows doctors to tailor the amount of immunosuppressant medications to each patient, rather than a “one-size-fits-all” approach that results in more side-effects, including low blood counts and increased risk of infection and cancer, he added.

Overall, more organs would be available for people on long wait lists, many of whom need time-consuming and physically draining dialysis to aid failing kidneys that can no longer rid their blood of toxins.

However, the advanced technology would introduce a new challenge when it comes to fairly allocating donated kidneys to those who have been on a wait list for years but do not end up being well-matched to an available organ.

“You can imagine a scenario where someone has been waiting for 10 years and they’re next on the wait list, but the organ is poorly matched and it goes to someone else who’s better matched but hasn’t waited as long,” said Lan, adding the wait-list system will have to be revamped to make it as fair as possible.

Patients under age 18 and those who have built up antibodies that could result in rejection are currently prioritized for a transplant, he said.

The rapid sequencing technology is being tested in British Columbia to refine the degree of achievable genetic compatibility between patients and donors while six other labs in the country are joining that effort, said Lan, adding that patients could start to be matched in about three years.

“Every single kidney transplant that we do will save the system a quarter million dollars per patient over five years,” said Lan.

Much of that comes from potentially ending costly dialysis treatments, which can reach about $100,000 per patient per year, and require three sessions a week for four hours, Lan said. The annual cost of medications and medical visits for transplant patients are about $20,000.

Nancy Verdin, 63, has had three kidney transplants — in 1988, 1992 and 1995 — but her immune system rejected all of them despite multiple immunosuppressant drugs.

“The reason I’m not getting a transplant now is because I do reject them, and it’s a terrible waste,” she said from Red Deer, Alta.

“Dialysis has kept me alive, but what I’m living with now is the long-term effects of dialysis. Your system just gets run down.”

She said better matches with a “precious resource” would offer a chance at a “normal life.”

“Even if it doesn’t become available to me, it certainly is so exciting to know that it could be available to other people,” Verdin said.

Lan said patients who have already had multiple failed transplants face a higher risk of rejecting future donor kidneys because their immune system has developed antibodies that mount a more aggressive attack against each subsequent new organ.

However, he did not rule out the possibility that “very complicated patients” could potentially be matched with a donor kidney.

“Oftentimes they have an urgency to get the next kidney transplant. But at least for their doctors looking after them, they will know with their eyes wide open, what’s the best decision for that patient. Is it best for them to accept the next kidney that comes along to get them off dialysis first or does it make sense for them to wait a little bit longer, knowing that they’re going to find a well-matched organ?”

The first kidney transplant, performed in the United States in the mid-1950s, involved identical twins whose genetic compatibility allowed for a matched donation without the need for immunosuppressant drugs, which were not available then.

“In a way, this is kind of like back-to-the-future in our field because we have medications and we don’t have to do identical transplants,” Lan said. “We can get as close as possible to that so that the immune system thinks the individuals are identical twins when they’re actually not.”

This report by The Canadian Press was first published June 4, 2024.

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