In a step toward increasing access to donor organs, scientists have converted a blood-type-A kidney to blood type O and then transplanted it into a brain-dead person.
The kidney, which had essentially been turned into a universal transplant organ, functioned well for two days before showing signs of rejection. With refinement, this strategy could pave the way for shorter waits on organ donor lists.
Kidney transplantation has been a treatment for patients with renal disease since the 1950s. Like all organ transplants, however, it is somewhat limited by the need to match the blood type of the donor with that of the recipient, along with the requirement to find an appropriately sized organ that’s geographically close enough to transplant in time.
Humans have four major blood groups — A, B, AB and O — and the immune system of a person with one blood type may react against another type. For example, a transplant candidate with type O blood can only receive a type-O donor kidney, but someone with A, B or AB blood type can also receive a type O kidney. That’s because each blood type is defined by immune-triggering substances, called antigens. O blood lacks these antigens, so it can be given universally, while other blood types would set off a type-O person’s immune system.
However, in the late 1980s, scientists developed a way to transplant ABO-incompatible (ABOi) organs — an organ from a donor with one blood type into a donor with an incompatible blood type — into recipients who needed them. But the process is demanding and takes several days. Then, in 2022, researchers developed an enzyme-based treatment protocol that can convert an organ into a “universal” transplant called enzyme-converted O, or ECO.
“The ECO process has been demonstrated for lungs,” study co-author Stephen Withers, a professor emeritus of biochemistry at the University of British Columbia, told Live Science in an email. “We hope it works for all other organs — it should!” (Earlier this year, a different research group reported converting a kidney using ECO, but they started with a blood-type-B kidney in their experiment.)
Withers was part of the 2022 team that converted lungs from type A to type O. But that team did not transplant the ECO lungs into a person in that proof-of-concept experiment. In the new study, Withers and colleagues used a type-A kidney that had been deemed unsuitable for transplantation and converted it to a type-O kidney by perfusing the kidney with a special fluid, which took about two hours.
“Perfusion devices and organ preservation solutions are quite commonly used to keep organs in good condition between donation and transplantation,” Withers explained. To convert the organ, the researchers put specific enzymes into the perfusion fluid that removed the blood-group antigens that can cause rejection.
“In this way, organs will not then get recognized and targeted by the anti-A antibodies present in the blood stream of the recipient,” Withers said. The procedure doesn’t permanently rid the organ of problematic antigens, but it could help stave off the worst of the immune system’s reaction.
To see whether the kidney could escape immediate rejection in a human, the team turned to a brain-dead recipient whose family consented to the study. The team transplanted the ECO kidney into the recipient, who carried a high quantity of anti-A antibodies.
In a typical transplant, antibody therapy is given to the recipient before and after the transplant to prevent “hyperacute” rejection, which happens quickly. But the research team wanted to test whether creating an ECO kidney would prevent early rejection, so they didn’t apply this therapy.
“We needed to understand how things progressed,” Withers said. They wanted to monitor the rate at which antigens reappeared in the kidney and for how long the recipient’s body could tolerate that reappearance.
The researchers found that the ECO kidney worked well for two days following transplantation, with no signs of rejection. Immune responses to the new kidney appeared on day three, which is when the ECO kidney began creating new A antigens.
“In an actual clinical transplant, there are a number of procedures that can be applied to minimize initial antibody-mediated rejection, including optimized immunosuppression,” Withers said. If these methods, which are standard care in any organ transplant, are also used for ECO kidneys, this could enable longer-term tolerance of the transplant.
Converting organs from one blood type to another is important for increasing patients’ access to donor organs, the researchers wrote in the study. This is particularly important for “type-O transplant candidates, who constitute over 50% of the waiting list and typically wait 2-4 years longer than do other blood types,” they wrote.
Although the ECO kidney was successfully transplanted, the development of this transplant process is still in its early stages.
“I do not know whether this will be applied universally,” Withers said. “However, it is certainly a possibility.”
This article is for informational purposes only and is not meant to offer medical advice.
