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

描述（由申请人提供）：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期和更好的生活质量。为了满足日益增长的肾脏移植需求，人们正在从老年和病情较重的供体那里采购肾脏。这导致捐赠肾脏的丢弃率更高，以及接受者的并发症更多，包括移植存活期更短。现有的临床模型预测移植肾质量的预测能力差，不能评估移植肾损伤的程度。然而，在接近采购时发生的同种异体移植物损伤可能会对移植受者造成严重后果：移植物功能延迟、同种异体移植物功能不良和移植物过早丢失的风险更大。 我们的建议是基于这样的假设，即在采购时在供体尿液和运输介质中测量的新的肾损伤生物标志物可以评估急性和慢性肾损伤，并且不同的生物标志物模式将预测同种异体移植物存活。我们将与四个器官采购组织合作，从1,000名连续死亡的捐赠者那里收集尿液样本，并为每个泵送的肾脏收集运输溶液样本。我们将测量五种急性损伤标志物和三种慢性损伤标志物。我们将通过与器官共享联合网络（UNOS）数据库的链接来确定所有患者的死亡率和移植物存活率。此外，我们将对500多名受者进行详细的图表审查，并将检查移植后两年内生物标志物与纵向移植物功能之间的关联。 早期、非侵入性和快速评估供体肾损伤可以推动更好的分配决策，并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物损伤的同种异体移植物和肾移植受者的治疗提供临床试验平台。

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.