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

描述(申请人提供)：与慢性透析相比，肾移植以较低的成本为受者提供了更长的生存时间和更好的生活质量。为了满足日益增长的肾移植需求，正在采购年长和病情较重的捐赠者的肾脏。这导致了更大的捐献肾脏丢弃率，以及更多的并发症，包括更短的同种异体移植存活时间。现有的预测移植肾质量的临床模型预测能力较差，并且不能评估移植肾损伤的程度。然而，同种异体移植物在获取时的损伤可能会给移植受者带来重大后果：移植物功能延迟、移植物功能不良和移植过早丧失的风险更大。我们的建议是基于这样的假设，即在采购时在供者尿液和运输介质中测量的新的肾损伤生物标记物可以评估急性和慢性肾损伤，并且不同的生物标记物模式将预测同种异体移植物的存活。我们将与四个器官采购组织合作，收集连续1000名已故捐赠者的尿液样本，并为每个移植的肾脏收集运输溶液样本。我们将检测5个急性损伤标志物和3个慢性损伤标志物。我们将通过连接到器官共享联合网络(UNOS)数据库来确定所有患者的死亡率和同种异体移植物存活率。此外，我们将对500多名受者进行详细的图表审查，并将在移植后两年内检查生物标记物和纵向移植物功能之间的关系。对供者肾脏损伤的早期、非侵入性和快速评估可以推动更好的分配决策，并有可能降低移植后并发症的发生率。此外，这些新工具可以为旨在改善同种异体移植损伤的同种异体移植和肾移植受者的治疗方法的临床试验提供一个平台。

DESCRIPTION (provided by applicant): Compared to chronic dialysis, kidney transplantation provides recipients with longer survival and better quality of life at a lower cost. In order to met increasing demands for kidney allografts, kidneys from older and sicker donors are being procured. This has led to greater discard rates of donated kidneys as well as more complications for recipients, including shorter allograft survival. Available clinical models to predict kidney allograft quality have poor prognostic ability and do not asses the degree of kidney allograft injury. However, allograft injury near the time of procurement can lead to major consequences for the transplant recipient: greater risks of delayed graft function, poor allograft function and premature loss of the transplant. Our proposal is based on the hypotheses that novel kidney injury biomarkers measured in donor urine and transport media at the time of procurement can assess acute and chronic kidney injury and that distinct biomarker patterns will predict allograft survival. In collaboration with four organ procurement organizations, we will collect urine samples from 1,000 consecutive deceased donors and samples of transport solution for every pumped kidney. We will measure five acute injury markers and three chronic injury markers. We will determine mortality and allograft survival in all patients by linkage to th United Network for Organ Sharing (UNOS) database. Additionally, we will perform a detailed chart review of over 500 recipients and will also examine associations between biomarkers and longitudinal graft function over two years after transplant. Early, non-invasive and rapid assessment of donor kidney injury could drive better allocation decisions and potentially reduce the rates of post-transplant complications. Further, these new tools could provide a platform for clinical trials of therapies for allografts and kidney transplant recipients aimed at ameliorating allograft injury.