Amid ongoing organ shortages and constraints in current transplant practices, researchers in Liège, Belgium, are investigating strategies to improve graft quality.

At a symposium held at CHU de Liège during International Liver Day, Tiago Pinto Coelho, a research fellow at the Laboratory of Translational Research in Nephrology, Metabolism, and Cardiovascular Biology at the GIGA Institute, ULiege, Liege, Belgium, presented work examining the cellular mechanisms of brain death to better understand renal graft viability.

Transplantation has remained the treatment of choice for end-stage kidney disease following surgical advances in the 1950s and the 1960s. “Why must we continue transplantation research? Quite simply because more and more patients are on the waiting list,” Pinto Coelho said. In 2025, 72 transplants were performed in Liège, including 71 from deceased donors.

However, the scale of these challenges remains substantial. “Last year, slightly fewer than two people a day died while on the waiting list without receiving a transplant,” he said.

Medical Urgency

To address this shortage, clinicians are increasingly using lower-quality organs. “They sometimes come from older donors with more comorbidities and therefore lead to delayed graft function in the postoperative period, affecting 35%-50% of recipients,” Pinto Coelho said. Delayed graft function was associated with almost double the risk for death and threefold the risk for immediate return to dialysis or return to the transplant waiting list.

Donor Types

In many countries, the preferred donors are those with brain death, referred to as donation after brain death (BDD), and donation after circulatory arrest/death (DCD), which are the two primary types of deceased organ donation. “Many clinicians remain reluctant to use this type of donor because of the warm ischemia inherent to this procurement process,” he noted.

Meta-analyses have shown that DCD grafts lead to more frequent delayed graft function than BDD grafts. However, “grafts from BDD that develop delayed graft function appear to have worse long-term outcomes than grafts from DCD with delayed graft function,” he said.

Current research has primarily focused on BDD. Transcriptomic analyses in animal models have shown that TNF alpha regulates approximately 60 genes that are directly involved in the pathophysiologic processes observed in these donors. Additional studies have confirmed that high circulating TNF levels are associated with lower renal function and poorer graft survival in recipients. The researchers concluded that TNF is central to the damage induced by brain death in kidney grafts.

Targeted Intervention

Researchers then evaluated whether administering the anti-TNF agent etanercept directly to donors after brain death could modify the injury processes. The intervention produced clear biologic effects. “Administering an anti-TNF reduces both the number and extent of lesions at the time of procurement,” Pinto Coelho said. Transcriptomic analysis showed that the injury signature was completely reversed in treated donors compared to that in untreated donors.

This approach is noteworthy because of its simplicity. The researcher highlighted the ability to act “in a very simple way by administering a drug that is very inexpensive, directly to the donor.” This strategy could “significantly improve graft quality” systematically.

Despite these encouraging cellular and histologic findings, its clinical benefits remain unproven. Pinto Coelho cautioned: “Having fewer lesions and a better-quality organ at the time of procurement does not mean there will be better function in the recipient.”

The next critical step expected “in the coming weeks is to perform actual transplants using grafts preconditioned with anti-TNF. Future clinical trials are needed to determine whether this strategy can reduce graft failure after transplantation.”

This story was translated from MediQuality, part of the Medscape Professional Network.