Using a new enzymatic technology, researchers transplanted a kidney with blood type A into a recipient with blood type O. (Image courtesy of Getty Images)
In a step toward expanding access to donor organs, scientists converted a kidney with blood type A into a kidney with blood type O and then transplanted it into a brain-dead person.
The kidney, which has effectively become a universal organ for transplantation, functioned normally for two days before showing signs of rejection. If improved, this strategy could reduce waiting times on organ donor lists.
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Kidney transplantation has been a treatment option for patients with renal failure since the 1950s. However, like any organ transplant, it has some limitations, including the need to match the donor's and recipient's blood types, as well as the need to find an organ of suitable size located close enough to the transplant site.
Humans have four main blood types—A, B, AB, and O—and the immune system of a person with one blood type can react to another. For example, a transplant candidate with blood type O can only receive a kidney with type O, but a person with A, B, or AB can also receive a kidney with type O. This is because each blood type is determined by immune-stimulating substances called antigens. O blood lacks these antigens, so it can be transfused to anyone, while other blood types activate the immune system of a person with type O.
However, in the late 1980s, scientists developed a method for transplanting ABO-incompatible (ABOi) organs—organs from a donor with one blood type to a donor with an incompatible blood type—to recipients in need. However, this process is labor-intensive and takes several days. Then, in 2022, researchers developed an enzyme-based treatment protocol that converts an organ into a “universal” transplant, called enzyme-converted O2 (ECO).
“The effectiveness of the IVF process has been demonstrated in the 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 will work for other organs as well—as it should!” (Earlier this year, another research team reported transforming a kidney using IVF, but they began their experiment with kidneys from people with blood type O.)
Withers was part of the 2022 team that transplanted lungs from type A to type O. However, in that pilot study, the team did not transplant lungs obtained through IVF into humans. In the new study, Withers and his colleagues used a kidney from type A, deemed unsuitable for transplant, and transplanted it into type O, perfusing the kidney with a special fluid. This process took about two hours.
“Perfusion devices and organ preservation solutions are often used to maintain organs in good condition between donation and transplantation,” Withers explained. To transform the organ, researchers add specialized enzymes to the perfusion fluid that remove blood type antigens that can cause rejection.
“This way, the organs won't be recognized and attacked by anti-A antibodies present in the recipient's bloodstream,” Withers said. The procedure doesn't permanently rid the organ of problematic antigens, but it can help prevent the most severe immune system response.
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To test whether a kidney could avoid immediate rejection in humans, the team approached a brain-dead recipient whose family had consented to the study. The team transplanted a kidney obtained through IVF into a recipient with high levels of antibodies to the A-antigen.
In a typical transplant, the recipient is given antibody therapy before and after the transplant to prevent “hyperacute” rejection, which develops quickly. However, the research team wanted to test whether creating an IVF kidney would prevent early rejection, so they did not use this therapy.
“We needed to understand how the processes unfold,” Withers said. They wanted to track the rate of antigen reappearance in the kidney and how long the recipient's body could tolerate this reappearance.
Researchers found that the IVF-transplanted kidney functioned well for two days after transplantation, with no signs of rejection. An immune response to the new kidney emerged on the third day, when the IVF-transplanted kidney began producing new A antigens.
“In real-world clinical transplantation, there are a number of procedures that can be used to minimize primary antibody-mediated rejection, including optimized immunosuppression,” Withers said. If these methods, which are standard treatment for any organ transplant, are also applied to kidney transplantation after IVF, this could lead to longer-lasting graft tolerance.
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The researchers note in their study that converting organs from one blood type to another is important for expanding patient access to donor organs. This is especially important for “transplant candidates with blood type O, who make up more than 50% of the waiting list and typically wait 2–4 years longer for a transplant than patients with other blood types,” they note.
Although the IVF kidney was successfully transplanted, the development of this transplant process is still in its early stages.
“I don't know if it will be used everywhere,” Withers said. “But it's certainly a possibility.”
Disclaimer
This article is for informational purposes only and does not contain medical advice.
Christina Killgrove, Social Link Navigation, Staff Writer
Christina Killgrove is a staff writer for Live Science, specializing in archaeology and paleoanthropology news. Her articles have also appeared in publications such as Forbes, Smithsonian, and Mental Floss. Christina holds a PhD in biological anthropology and an MA in classical archaeology from the University of North Carolina, as well as a BA in Latin from the University of Virginia. She previously worked as a university professor and researcher. She has received awards for her research from the Society for American Archaeology and the American Anthropological Association.
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