Novel Kidney Injury Tools in Deceased Organ Donation to Predict Graft Outcomes

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Efforts to meet the increasing need for kidney transplantation have resulted in more kidney procurements from older and sicker donors, but have also unfortunately led to greater discard rates of procured kidneys. Although a subset of these organs are unsuitable for transplantation, many kidneys are unnecessarily discarded due to the inability to accurately assess graft quality and predict graft outcomes, often driven by unfavorable scores on the kidney donor profile index (KDPI), a widely used but inadequate metric for evaluating the quality of donated kidneys. The objective of the Deceased Donor Study is to gain insight into the biological processes that affect kidney quality during donor death and organ procurement. Phases 1 and 2 of the study generated novel insights into donor pathophysiology and revealed limitations in organ quality assessment, which motivate this renewal application. After evaluating >30 urine biomarkers collected from >1,500 donors, a protective effect for increasing donor urinary levels of repair biomarkers (e.g., YKL-40, uromodulin, and osteopontin), on long- term graft function in >2,500 recipients was demonstrated. In phase 3, these urinary repair biomarker results will begin to be validated and implemented in organ allocation process using real-time point-of-care tests. In collaboration with organ procurement organizations, repair biomarkers in samples from 500 donors with acute kidney injury (AKI) or high-risk KDPIs will be measured prospectively on site. Additional racial diversity will be included in our cohort in collaboration with the multicenter APOL1 Long- term Kidney Transplantation Outcomes Network to assess the differential response in recipient allograft outcomes to the APOL1 genotype more commonly present in Black donors. Lastly, in collaboration with the United Network for Organ Sharing laboratory, “adjusted” KDPIs will be provided for donors with AKI based on creatinine trajectory, genetic risk variants, and biomarker information, with the aim of improving kidney acceptability. These new tools may also provide a platform for enhancing understanding of the natural history of deceased-donor kidney transplantation, advancing the science of renal injury and repair as it relates to donor race, and determining the best approaches for transplanting kidneys at risk for discard.