Canadian and Chinese researchers have completed the world's first transplant of a kidney with a modified blood type. The organ, converted from type A to type O using special enzymes, was transplanted into a brain-dead patient in Chongqing. There was no rejection for two days, only a mild reaction on the third. The technique, published in Nature Biomedical Engineering, could dramatically shorten waiting lists for those awaiting a kidney transplant.
How blood-changing enzymes work
Blood type antigens are molecular labels on the surface of cells. In the case of type A blood, there is a specific sugar that the immune system of those with type O recognizes as foreign and attacks. Stephen Withers e Jayachandran Kizhakkedathu,University of British Columbia, have spent over a decade developing enzymes capable of removing these sugars. Molecular scissors that cut away the A label, exposing the underlying O type.
"It's like stripping the red paint off a car and revealing the neutral base underneath," Withers explains. "Once that's done, the immune system no longer sees the organ as foreign."
The procedure takes place during the hypothemic perfusion, the phase in which the organ is kept alive outside the body with a device that pumps special fluidsThe enzymes are added to the perfusion fluid and work for about two hours. Low concentrations, high selectivity. Eventually, the type A kidney became type O.
The first test on a human being
The transplant took place in Chongqing, China, on a 68-year-old man who had been declared brain dead. The family had given consent for the body to be used in research. The recipient had blood type O with a high concentration of anti-A antibodies: exactly the worst-case scenario for testing a converted type A organ.
In standard transplants, hyperacute rejection can destroy an incompatible organ within minutesThe recipient's antibodies immediately attack the foreign antigens, triggering a cascade reaction that blocks the blood vessels and kills the organ. This didn't happen here. For 48 hours, the kidney functioned normally: it filtered blood, produced urine, and maintained all its parameters within normal limits.
On the third day, some group A markers reappeared on the organ's surface. The body began to produce an immune response, but much weaker Compared to a classic rejection, the researchers observed complement deposits and antibody-mediated lesions, but the damage was limited. The kidney continued to produce urine until the sixth day.
“This is the first time we've seen this in a human model,” Withers says. “It gives us valuable insights into how to improve long-term outcomes.” The enzymatic conversion isn't permanent: some A antigens regenerate over time. But This first experiment demonstrates that immediate rejection can be avoided, and that subsequent reactions are manageable with standard immunosuppressive protocols.
The problem of waiting lists
Someone with blood type O is a universal donor: their organs are suitable for everyone. But they can only receive from other type O donors. The result is a cruel paradox: Over 50% of people on the waiting list for a kidney transplant have blood type O, and wait 2 to 4 years longer than those with other blood types..
In Italy, the situation is slightly better thanks to the single regional list, but the numbers remain significant. From 2002 to 2022, 45.066 patients were enrolled on the kidney transplant waiting list. Fifty percent are transplanted within two years, but for those with type O blood, the waiting time is longer. In 2024, Italy recorded a record 4.692 total transplants, 2.110 of which were from deceased donors. But demand still exceeds supply.
If the ECO (enzyme-converted organ) technique worked on a large scale, any type A, B, or AB organ could become type O. Waiting lists for type O patients would be dramatically shortened. And doctors could focus on other immunological compatibility, which determines the long-term survival of a transplant.
From the 2019 discovery to human testing
The Vancouver team had identified the two key enzymes in 2019Highly active, selective, effective at very low concentrations. In 2022 A group in Toronto had demonstrated that lungs could be converted from type A to type O, but without transplanting them into anyone. The definitive test was needed: a converted organ inside a human body.
The turning point has arrived at the end of the 2023Kizhakkedathu was traveling abroad when the Chinese collaborators showed him the data. “They had converted a human kidney and transplanted it into a brain-dead recipient. It worked beautifully.” He called Withers in the early hours of the Canadian morning. “I was elated. It was a dream moment.”
What happens now
The next step is clinical trials on living patients. The startup Avivo Biomedical, a spin-off of the Canadian university, will lead the development of the technology for applications in transplantation and transfusion medicine. The idea is to create universal blood on demand using the same enzymes.
Natasha Rogers, transplant clinic at Westmead Hospital from Sydney, calls the results "revolutionary" (sorry, but she says that, not me). "Treating the donor organ instead of the recipient is a breakthrough. The study demonstrates that the same immunosuppression can be used as in transplants between matched groups."
Open questions remain. The regeneration of A antigens on day three suggests that protocols will need to be developed to prolong the enzymes' effect or combine conversion with more targeted immunosuppressive therapies. Other approaches, such as genetically modified pig xenotransplants, continue in parallel.
But this technique has one advantage: works with human organs from deceased donors, without requiring days of recipient preparation. Desensitizing the patient with plasmapheresis and antibody depletion, expensive and risky procedures that increase infections and perioperative complications, is no longer necessary. We treat the organ, not the person.
The Type O Paradox
There's an irony in all this. Blood type O is considered "primitive" from an evolutionary perspective: it lacks the A and B antigens because they were never added. Now we discover that we can go back, remove what evolution added, and make any organ compatible with anyone.
“This is what it feels like when years of basic science finally connect to patient care,” says Withers. “Seeing our discoveries come closer to real-world impact is what drives us forward.”
For now, it's an experiment. In a few years, perhaps, it will become routine. And waiting lists, that paradigm in which someone must die so that someone else can live, might become a little less cruel.
