Skip to main content
Premium Trial:

Request an Annual Quote

Post-Transplant Diabetes Risk Informed by Polygenic Risk Profiles in Donors, Recipients

NEW YORK – Taking organ donor and recipient genetics into consideration — via a polygenic risk score (PRS) — may help identify individuals at risk of developing diabetes after a solid organ transplant.

"Our study demonstrates the importance, and the potential application, of PRS in solid organ transplantation," co-first and corresponding author Abraham Shaked, a researcher at the University of Pennsylvania's Penn Transplant Institute, and his coauthors wrote in Nature Medicine on Thursday.

In an email, Shaked noted that the transplant setting is especially amenable for PRS application testing, since diabetes tends to develop relatively shortly after transplantation — within six months or a year — in affected organ recipient individuals.

The researchers focused on four groups of organ donors and recipients, including 1,581 liver recipients, 1,555 liver donors, 2,062 kidney transplant recipients, and 533 corresponding kidney donors, looking at the ways that variants in an established type 2 diabetes (T2D) PRS tracked with pre-transplant diabetes and with post-transplant diabetes mellitus (PTDM) in donors and recipients.

"We applied this T2D PRS to liver and kidney transplantation, with the aim of determining the association of recipient and/or donor genetics, both independently and in concert, with the development of PTDM," the authors explained. "Quantifying T2D PRS in transplant candidates may be used to personalize immunosuppression … and to risk-stratify those who may benefit from aggressive treatment such as dieting, glucose monitoring, and insulin therapy."

Based on their findings, the authors suggested that "T2D PRS as a clinical predictive assay could lead to personalized treatment strategies, with an aim to reduce the occurrence of PTDM."

As expected, the T2D PRS corresponded with the risk of T2D development prior to organ transplantation in the organ recipient individuals, for example.

But the team also saw ties between the T2D PRS and PTDM development in the organ recipients. Likewise, some recipients appeared more prone to PTDM when the individuals donating their organs had risky T2D PRSs, specifically in the context of liver donation.

"We are used to thinking about the transplant setting as transferring immune-related genetics that is impacting rejection," Shaked explained, but the risk of transferring a condition such as diabetes is not typically considered.

"This is the first time we are introducing the concept that other issues should be considered when discussing donor-recipient genetic interactions," he said. "This should be very relevant to how to design management of the transplant recipient and [provides] different views [of] how to look at the donor."

In their analyses, the researchers demonstrated that the combined donor-recipient T2D PRS could significantly improve PTDM risk prediction in the liver transplant context compared to models that focused on established clinical factors, for example.

In particular, donor-recipient pairs falling into the highest risk T2D PRS group appeared to be more than three times as likely to include recipients who developed PTDM than liver transplant recipients from donor-recipient pairs classified as the lowest risk with the T2D PRS approach.

Together, such findings support the notion that the T2D PRS "identifies transplant candidates with high risk of PTDM for which pre-emptive diabetes management and donor selection may be warranted," the authors wrote, adding that "the same approach could be used to explore the impact of donor and recipient genetics on the development of other morbid complications that influence long-term recipient survival; for example, chronic kidney disease."