Fawaz_2025_TNF_luminex_data.xlsx

Kidney transplantation is the best treatment for end-stage kidney disease as it improves life-expectancy and quality of life. Deceased donation following brain death and after circulatory death are the main source of transplants. Deceased donation, with a sequence of donor management and organ procurement steps, may contribute to donor organ injury through triggering systemic inflammation. Despite the important clinical implications, the impact of donor circulating inflammation on kidney function and short- and long-term posttransplant outcomes are unknown. In this study, we profiled tumor necrosis factor alpha (TNFα), and receptors TNFR1 and TNFR2 levels in 945 longitudinal plasma samples, including a validation cohort, collected during donor management of 523 deceased and 34 living donors from multiple centres across the United Kingdom. We demonstrated that during donor management, longitudinal TNF profiles were donor type specific. High donor TNFα plasma levels during donor management were independently associated with inferior 12 months and up to 96 months reduced graft function and survival in recipients. Deceased donors with high levels of circulatory TNFα had increased kidney expression of markers of inflammation and apoptosis prior to retrieval. Further <i>in vitro</i> investigations confirmed that donor plasma rich in TNFα promoted inflammation in human podocytes through TNFR1 signaling, a response that was ameliorated by infliximab, a TNFα specific neutralising antibody. Thus, our study suggests that monitoring plasma inflammation levels offers the potential to better assess and optimize deceased donor kidneys pretransplant, providing opportunities to improve donor kidney quality and extend graft longevity in recipients.