Researchers at the University of Cambridge have successfully altered the blood type on three deceased donor kidneys in a ground-breaking discovery that could have major implications for kidney patients.
The project, funded by charity Kidney Research UK, could increase the supply of kidneys available for transplant, particularly within ethnic minority groups who are less likely to be a match for the majority of donated kidneys.
Professor Mike Nicholson and PhD student Serena MacMillan used a normothermic perfusion machine – a device which connects with a human kidney to pass oxygenated blood through the organ to better preserve it for future use – to flush blood infused with an enzyme through the deceased kidney.
The enzyme acted like “molecular scissors” to remove the blood type markers that line the blood vessels of the kidney resulting in the organ being converted to the most common O type.
A kidney from someone with an A blood type cannot be transplanted to someone with a B blood type, nor the other way around. But changing the blood type to the universal O will allow more transplants to take place as O can be used for people with any blood group.
“Our confidence was really boosted after we applied the enzyme to a piece of human kidney tissue and saw very quickly that the antigens were removed,” said MacMillan.
“After this, we knew that the process is feasible, and we just had to scale up the project to apply the enzyme to full-size human kidneys. By taking B type human kidneys and pumping the enzyme through the organ using our normothermic prefusion machine, we saw in a matter of just a few hours that we had converted a B type kidney into an O type.”
The discovery could be particularly impactful for people from ethnic minority groups who often wait a year longer for a transplant than Caucasian patients.
People from minority communities are more likely to have B type blood and with current low donation rates from these populations, there are simply not enough kidneys to go around. In 2020/21, just over 9% of total organ donations came from black and minority ethnic donors whilst black and minority ethnic patients make up 33% of the kidney transplant waiting list.
The Cambridge team now need to see how the newly changed O type kidney will react to a patient’s usual blood type in their normal blood supply. The perfusion machine allows them to do this before testing in people, as they can take the kidneys which have been changed to the O type, use the machine to introduce different blood types and monitor how the kidney might react, simulating the process of transplant into the body.
One of the biggest restrictions to who a donated kidney can be transplanted to is the fact that you have to be blood group compatible,” said Nicholson, professor of transplant surgery.
“The reason for this is that you have antigens and markers on your cells that can be either A or B. Your body naturally produces antibodies against the ones you don’t have.
“Blood group classification is also determined via ethnicity and ethnic minority groups are more likely to have the rarer B type. After successfully shifting blood group to the universal O type, we now need to look at whether our methods can be successful in a clinical setting and ultimately carried through to transplantation.”
Dr Aisling McMahon, executive director of research at Kidney Research UK said: “The research that Mike and Serena are undertaking is potentially game-changing. It is incredibly impressive to see the progress that the team has made in such a short space of time, and we are excited to see the next steps.
“As an organisation, we are committed to funding research that transforms treatments and tackles health inequalities. We know that people from minority ethnic groups can wait much longer for a transplant as they are less likely to be a blood-type match with the organs available. This research offers a glimmer of hope to over 1,000 people from minority ethnic groups who are waiting for a kidney,” McMahon said.
After testing the reintroduction of other blood types, the team in Cambridge will look at how the approach might be used in a clinical setting. Having made great progress in such a short space of time they are hopeful for the future.
The full paper on Mike and Serena’s work is set to be published in the British Journal of Surgery in the coming months.