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

满足日益增长的肾移植需求的努力导致了更多的 从年长和病情较重的捐赠者那里获取肾脏，但不幸的是也导致了 获得的肾脏的报废率更高。尽管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果，通常是由 肾捐赠者概况指数(KDPI)得分不佳，这是一种广泛使用的但 用于评估捐赠肾脏质量的指标不充分。该计划的目标是 已故捐献者研究是为了深入了解影响肾脏的生物过程 捐献者死亡和器官获取期间的质量。研究的第一阶段和第二阶段 对捐赠者的病理生理学产生了新的见解，并揭示了器官的局限性 质量评估，这是这次续签申请的动力。在评估&gt；30尿液后 从1500名捐赠者身上收集的生物标记物对增加捐赠者的保护作用 尿修复生物标志物(如YKL-40、尿调蛋白和骨桥蛋白)水平 在2500名受者中显示了足月移植物功能。在第三阶段，这些尿液 修复生物标志物的结果将开始在器官分配中得到验证和实施 使用实时护理点测试的流程。与器官采购合作 组织，修复500名急性肾损伤捐赠者样本中的生物标记物 (AKI)或高风险KDPI将在现场进行前瞻性测量。额外的种族问题 多样性将与多中心APOL1 Long-1合作纳入我们的队列 TERM肾移植结局网络评估不同患者的反应 APOL1基因在黑人中常见的同种异体移植结果 捐赠者。最后，与器官共享联合网络实验室合作， “调整后的”KDPI将根据肌酐轨迹为AKI的捐赠者提供， 遗传风险变异和生物标记物信息，目的是改善肾脏 可接受性。这些新工具还可以提供一个增进理解的平台 了解已故供者肾移植的自然史，推动科学进步 肾脏损伤和修复，因为它与供者种族有关，并确定最佳 有可能被丢弃的肾脏移植方法。

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.