The first successful human transplant of a kidney enzymatically converted from blood type A to universal type O may mark a pivotal shift in transplantation. In a study published in Nature Biomedical Engineering, researchers reported perfusing a donor kidney with enzymes that removed A antigens and transplanting the organ into a brain-dead recipient with family consent to observe the immune response in real time.

Study investigator Jayachandran Kizhakkedathu, PhD, of the University of British Columbia (UBC) in Vancouver, British Columbia, Canada, said the process leverages standard ex vivo perfusion devices used to preserve organs between donation and transplantation.

“The actual process for conversion is very simple as it takes advantage of currently employed perfusion technology for transplantation,” Kizhakkedathu told Medscape Medical News. Enzymes are added to the perfusion fluid to clip the A antigens from the organ surface. Before implanting the kidney, the team then replaced the perfusion fluid with fresh fluid (not containing enzymes) to flush out residual enzymes.

“This technology could indeed be easily implemented worldwide once, of course, it has received proper regulatory approval after considerable further testing,” added Kizhakkedathu, a professor in the Department of Pathology and Laboratory Medicine and the Centre for Blood Research at UBC.

Changing the Donor Organ, Not the Patient

Traditional methods for overcoming blood type incompatibility in transplants require days of antibody removal and intensive immunosuppression for the recipient. In contrast, this new approach changes the organ rather than the patient, potentially allowing for faster procedures with fewer complications.

In this first human case, the converted graft was well tolerated. There was no evidence of antibody-mediated rejection for 2 days post-transplant. On the third day, however, antibody-mediated lesions and complement deposition emerged alongside A-antigen regeneration, and later higher Banff scores, suggesting an immune-mediated response.

“Blood type antigens act like nametags on cells, and the UBC enzymes act as molecular scissors, snipping off the ‘nametag’ that marks type A and revealing type O beneath,” Kizhakkedathu said. While emphasizing that further optimization and controlled clinical trials are needed, he added that they “believe this to be a game-changing technology in transplantation that will increase the availability of organs through improving the probabilities of finding a match by removing the need to consider blood type, only requiring HLA (human leukocyte antigen) match.”

A Donor-Centric Approach

Kidney transplants are already performed across the ABO barrier but only in select circumstances, such as when the antigen and antibody titers are low.

“Our protocol flips the script since it is a donor-centric procedure, which only takes approximately 1 hour,” Kizhakkedathu said. “It can therefore be used with both living donors and deceased donors. Not only will this technology save lives but also it will result in great healthcare savings.”

Currently, those on waiting lists are kept alive by dialysis, a process that is not only very taxing but also quite expensive. Regulatory approval for clinical trials is the next hurdle. Avivo Biomedical, a partner UBC spin-off company, is leading the development of these enzymes for transplant application. Kizhakkedathu, along with co-authors Peter Rahfeld and Stephen G. Withers, are founders of Avivo Biomedical Inc.

Challenges and Questions Remain

Takayuki Hirose, MD, PhD, assistant professor in the Department of Urology at Hokkaido University in Sapporo, Japan, who was not involved in the study, noted that the reappearance of some blood type markers within days highlights a key challenge.

“This observation raises a question: Does a patient need additional immunosuppressants to prevent rejection triggered by those markers?” Hirose told Medscape Medical News.

However, he added that the technique has revolutionary implications if it can be applied to remove HLA antigens.

“This approach has the potential to induce tolerance, which means a patient does not need to take immunosuppressants without caring about risk of rejection. It would be a Holy Grail.”

Kizhakkedathu, along with co-authors Peter Rahfeld and Stephen G. Withers, reported being founders of Avivo Biomedical Inc., which is commercializing the enzymes described, and inventors on a patent application submitted by UBC. The other coauthors declared having no competing interests. Hirose had no financial disclosures.

John Schieszer, MA, is an award-winning national journalist and podcast broadcaster of The Medical Minute. He can be reached at medicalminutes@gmail.com.