November 2022 Issue 05 www.renalinterventions.net
In this issue:
Highlights from VASBI 2022 page 5
Kidney transplantation in focus page 8
John Aruny page 12
Addressing “the big questions” with KDOQI page 15
UK researchers alter blood type of deceased donor kidneys in “potentially game-changing” breakthrough
Higher risk of allcause mortality found in female patients after starting dialysis Compared with male patients, female patients have been found to have a higher risk of all-cause mortality in the first five years postdialysis initiation—a difference driven by higher mortality from infections and dialysis withdrawals. T H E S E F I N DI N G S H AV E B E E N published in the American Journal of Kidney Diseases (AJKD) by Wai Lim (Sir Charles Gairdner Hospital, Perth, Australia) and colleagues. The authors note that higher early mortality rates on dialysis have, at times, been observed among female patients compared to their male counterparts. However, discrepancies in cause-specific mortality between male and female incident dialysis patients are “not well understood” and, as such, Lim et al set out to elucidate this further via a retrospective cohort study. Their cohort included incident patients who had initiated dialysis in Australia and New Zealand from 1998–2018. The key outcomes of their analysis were cause-specific and all-cause mortality on dialysis. The researchers also note that they censored for kidney transplantation, and applied adjusted, cause-specific, proportional hazards models, focusing on the first five years following initiation of dialysis. Among 53,414 patients (39% female), followed for a median period of 2.8 years, 27,137 (51%) died, with the predominant cause of death being attributed to cardiovascular disease (CVD, 18%) followed by dialysis withdrawal (16%). Compared to male patients, female patients were more likely to die in the first five years after dialysis initiation (adjusted hazard ratio [aHR] of 1.06). And, Lim et al report, while female patients experienced a lower risk of CVD-related mortality (aHR 0.93) compared to male patients, they experienced a greater risk of infection-related (aHR 1.20) and dialysis withdrawal-related (aHR 1.19) mortality. After acknowledging the possibility of residual and unmeasured confounders as a potential limitation, the authors conclude that their research could help to inform the study of sex differences in mortality in other geographic settings.
Profile:
Researchers at the University of Cambridge (Cambridge, UK) have successfully altered the blood type of three deceased donor kidneys—a breakthrough with major implications for the future of kidney care.
T
Follow Renal Interventions on all our social media platforms for the latest news, insight and events in kidney care
his was achieved under a Kidney Research UK-funded project that, according to the researchers, could increase the supply of kidneys available for transplant, particularly within ethnic minority groups who are less likely to be a viable match for the majority of donated kidneys. Professor of Transplant Surgery Mike Nicholson and PhD student Serena MacMillan (both University of Cambridge) used a normothermic perfusion machine—a device that passes oxygenated blood through a human organ to better preserve it for future use—to flush blood infused with an enzyme through the deceased kidneys. The enzyme acted like “molecular scissors” to remove the blood type markers that line the kidney’s blood vessels, resulting in the organ being converted to the most common O blood type. This is significant because, while an A-type donor kidney cannot be transplanted to a B-type recipient, or vice versa, kidneys from universal O-type donors can be used in patients of any 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 perfusion machine, we saw in a matter of just a few hours that we had converted a B-type kidney into an O type.” This discovery could be particularly impactful for ethnic minority groups who often wait a year longer for a transplant than Caucasian patients, as per the University of Cambridge. And, in 2020/21, just over 9% of total organ donations came
from Black and minority ethnic donors, O-type while these kidneys offer patient groups a universal make up 33% of transplant kidney transplant option waitlists, which is thought to be a result of such populations generally being less likely to be a bloodtype match with the available supply of organs. 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 newly altered O-type kidneys, use the device to introduce different blood types, and monitor how the kidney might react, simulating the process of transplantation into the body. “One of the biggest restrictions [on] who a donated kidney can be transplanted to is the fact that you have to be blood-group compatible,” said Nicholson. “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.” Kidney Research UK executive director of research Aisling McMahon described this breakthrough as “potentially game-changing”, offering “a glimmer of hope” to the hundreds of minority ethnic groups waiting for a kidney. A full paper detailing the Cambridge team’s work is now set to be published in the British Journal of Surgery.
“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.”