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

为了满足日益增长的肾移植需求， 从老年人和病情较重的捐赠者那里获得肾脏，但不幸的是， 获得的肾脏的丢弃率更高。虽然这些器官的一个子集是 由于不适合移植，许多肾脏被不必要地丢弃 无法准确评估移植物质量和预测移植物结局，通常由 肾供体档案指数（KDPI）评分不利，KDPI是一种广泛使用的，但 评估捐赠肾脏质量的指标不足。的目的 已故捐赠者研究是为了深入了解影响肾脏的生物学过程 捐赠者死亡和器官获取过程中的质量。研究的第1阶段和第2阶段 对供体病理生理学产生了新的见解，并揭示了器官移植的局限性。 质量评估，这激发了这种更新应用程序。评估后> 30尿 从> 1，500名供体收集的生物标志物，对增加供体的保护作用 修复生物标志物的尿水平（例如，YKL-40、尿调蛋白和骨桥蛋白），对长- 在> 2，500例受者中证实了移植物功能。在第三阶段，这些尿 修复生物标志物结果将开始验证并在器官分配中实施 使用实时护理点测试的过程。与器官采购合作 组织，修复来自500名急性肾损伤供体样本中的生物标志物 (AKI)或高风险KDPI将在现场进行前瞻性测量。其他种族 多样性将包括在我们的队列与多中心APOL 1长- 长期肾移植结果网络，以评估不同的反应， 黑人中APOL1基因型的受体同种异体移植物结局更常见 捐助者。最后，在与器官共享联合网络实验室的合作下， 将根据肌酐轨迹为AKI供体提供"调整后" KDPI， 遗传风险变异和生物标志物信息，目的是改善肾脏 可接受性这些新工具也可能为增进了解提供一个平台 死亡供体肾移植的自然史， 肾损伤和修复，因为它涉及到捐助者的种族，并确定最好的 移植肾脏的方法有被丢弃的风险。

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.