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

死亡器官捐赠中预测移植结果的新型肾损伤工具

• 批准号: 10583688
• 负责人: Chirag R Parikh
• 金额: $ 77.67万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583688
• 关键词: APOL1 gene; Acute Renal Failure with Renal Papillary Necrosis; Admission activity; Affect; Algorithms; Allografting; Biological Markers; Biological Process; Biology; Black race; Cessation of life; Clinical Data; Cohort Studies; Collaborations; Creatinine; Devices; Enrollment; Epidemiology; Evaluation; Failure; Functional disorder; Funding; Genetic; Genetic Models; Genetic Risk; Genotype; Hospitalization; Incidence; Inferior; Injury; Injury to Kidney; Kidney; Kidney Transplantation; Knowledge; Laboratories; Measurement; Measures; Methods; Natural History; Organ; Organ Donations; Organ Procurements; Outcome; Patients; Phase; Phenotype; Predisposition; Prevalence; Process; Race; Renal function; Reperfusion Injury; Research; Resources; Risk; Sampling; Science; Serum; Site; System; Time; Translational Research; Transplantation; UMOD gene; United Network for Organ Sharing; United States National Institutes of Health; Urine; Waiting Lists; cohort; delayed graft function; experimental arm; graft failure; graft function; high risk; improved; indexing; injury and repair; insight; lateral flow assay; novel; novel strategies; organ allocation; osteopontin; patient population; point of care; point of care testing; predictive modeling; prospective; protective effect; racial diversity; rapid testing; repaired; response; risk variant; tool; transplant centers; urinary

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.

满足肾脏移植需求越来越多的努力导致了更多 来自年长和病态捐助者的肾脏采购，但不幸的是 更大的丢弃肾脏的率。尽管这些器官的一个子集是 不适合移植，许多儿童是由于 无法准确评估成绩质量并预测通常由 肾脏捐赠者概况指数（KDPI）的分数不佳，这是一种广泛使用但 评估捐赠肾脏质量的度量不足。目的 已故的捐助者研究是为了深入了解影响肾脏的生物学过程 捐赠者死亡和器官采购期间的质量。研究的第1阶段和第2阶段 产生了对供体病理生理学的新见解，并揭示了器官的局限性 质量评估，这动机了此更新应用。评估> 30尿后 从> 1,500个捐助者那里收集的生物标志物，这是增加供体的受保护效果 修复生物标志物的尿液水平（例如，YKL-40，尿液统治和骨桥蛋白），长期 证明了> 2,500名接收者的术语移植功能。在第3阶段，这些尿液 维修生物标志物结果将开始在器官分配中验证和实施 使用实时保健测试的过程。与器官采购合作 组织，修复来自500名急性肾脏损伤捐赠者样品的生物标志物 （AKI）或高风险KDPI将在现场进行前瞻性测量。其他种族 多样性将与多中心APOL1长期合作包含在我们的队列中 术语肾脏移植结果网络，以评估 接受APOL1基因型的接受者同种异体结果更常见于黑色 捐助者。最后，与联合器官共享实验室合作， 将为基于肌酐轨迹的AKI提供“调整后的” KDPI， 遗传风险变体和生物标志物信息，目的是改善肾脏 可接受性。这些新工具也可能提供一个平台来增强理解 在死去的肾脏移植的自然历史上，推进了科学 与捐助者种族有关的肾脏伤害和维修，并确定最好的 移植有丢弃风险的孩子的方法。