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

项目摘要 与慢性透析相比，肾移植为受者提供了更好的生存率 以更低的成本提高生活质量。为满足日益增长的需求， 从年老体弱的捐赠者身上摘取肾脏不幸的是，这些努力导致了 移植肾的废弃率更高，移植肾的并发症更多， 包括同种异体移植物功能降低。预测同种异体移植物质量的现有工具 预后能力，不能充分评估肾损伤的程度或修复潜力， 采购等然而，早期同种异体移植物损伤可导致受体的严重后果， 例如移植物功能延迟、长期同种异体移植物功能差和过早移植的风险更大。 移植失败。 我们的建议是基于这样的假设，即新的损伤、炎症和炎症的生物标志物， 在采购时通过供体尿液和运输介质测量的修复将确定 不同的和信息模式，将预测同种异体移植物的生存。与五个合作 在研究的第1阶段，我们收集了来自器官采购组织的尿液样本， 超过1500名连续死亡的捐赠者和来自每个泵送肾脏的灌注液样本， 测量了几种肾损伤生物标志物。我们将这些捐赠者的所有接受者联系起来（超过 2500人）在联合国器官共享网络（UNOS）数据库，以确定 死亡率和同种异体移植物存活率。在第二阶段，我们将测量17种有前途的新生物标志物， 代表各种生物过程的生物储存库样本。我们将扩大 将子队列纳入1000多名接受者，以丰富重要事件的发生率 免疫学结果（即，急性排斥和进行性同种异体免疫），并收集详细的 关于移植物功能、免疫抑制和特定并发症的纵向数据 移植后5年，通过详细的图表审查。总共测量了25个以上的 生物标志物，额外的临床事件，更长的随访时间和创新的统计方法，我们 将创建多标记面板来评估供体肾脏质量并预测关键结果。 对供体生物过程的早期、非侵入性和快速评估可以更好地推动 分配决定和减少移植后并发症。这些新工具还可以 为肾移植和受体的治疗试验提供平台，旨在改善 损伤，增强恢复和改善长期同种异体移植物功能和存活。

Project Summary Compared to chronic dialysis, kidney transplantation provides recipients with better survival and quality of life at much lower cost. Efforts to meet the increasing need have resulted in more kidney procurements from older and sicker donors. Unfortunately, these efforts have led to greater discard rates of procured kidneys and more complications for allograft recipients, including reduced allograft function. Available tools to predict allograft quality have poor prognostic ability and do not adequately asses the degree of kidney injury or repair potential at procurement. However, early allograft injury can lead to major consequences for the recipient, such as greater risks of delayed graft function, poor long-term allograft function and premature loss of the transplant. Our proposal is based on the hypotheses that novel biomarkers of injury, inflammation and repair measured in donor urine and transport media at the time of procurement will identify distinct and informative patterns that will predict allograft survival. In collaboration with five organ procurement organizations for Phase 1 of the study, we collected urine samples from over 1500 consecutive deceased donors and perfusate samples from every pumped kidney and measured several kidney injury biomarkers. We linked all recipients from these donors (over 2500 individuals) in the United Network for Organ Sharing (UNOS) database to determine mortality and allograft survival. In Phase 2, we will measure 17 promising novel biomarkers from our biorepository samples that represent various biological processes. We will expand the Recipient Subcohort to include over 1000 recipients to enrich the event rates for important immunological outcomes (i.e., acute rejection and progressive alloimmunity) and collect detailed longitudinal data about allograft function, immunosuppression, and specific complications for up to 5 years after transplant via detailed chart review. With a total of over 25 measured biomarkers, additional clinical events, longer follow-up, and innovative statistical methods, we will create multi-marker panels to assess donor kidney quality and predict critical outcomes. Early, non-invasive and rapid assessment of donor biological processes could drive better allocation decisions and reduce post-transplant complications. These new tools could also provide a platform for therapeutic trials in kidney allografts and recipients aimed at ameliorating injury, augmenting recovery and improving long-term allograft function and survival.