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

死亡器官捐赠中预测移植结果的新型肾损伤工具

• 批准号: 8370601
• 负责人: Chirag R Parikh
• 金额: $ 75.8万
• 依托单位: YALE 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 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8370601
• 关键词: Acute; Age; Albumins; Allografting; Asses; Biological Markers; Biometry; Biopsy; Brain Death; Characteristics; Chronic; Chronic Kidney Failure; Clinical; Collaborations; Comorbidity; Creatinine; Data; Databases; Determination of Death; Dialysis procedure; End stage renal failure; Epidemiology; Failure; Fatty Acid-Binding Protein 1; Future; Gelatinase A; Glomerular Filtration Rate; Graft Survival; Growth; Histology; Histopathology; Hospitalization; Immunosuppression; Individual; Inflammatory; Injury; Interleukin-18; Kidney; Kidney Transplantation; Lead; Link; Measures; Modeling; Organ Donations; Organ Procurements; Outcome; Pathology; Patients; Pattern; Perfusion; Process; Pump; Quality of life; Risk; Sampling; Severities; Shipping; Ships; Solutions; Testing; Therapy Clinical Trials; Time; Transforming Growth Factor beta; Translational Research; Transplant Recipients; Transplantation; UMOD gene; United Network for Organ Sharing; Urine; Validation; Warm Ischemia; base; biobank; clinical practice; cohort; cost; delayed graft function; follow-up; graft failure; graft function; hemodynamics; implantation; improved; kidney allograft; meetings; mortality; novel; post gamma-globulins; premature; prognostic; prospective; rat KIM-1 protein; research study; tool; urinary

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. PUBLIC HEALTH RELEVANCE: Kidney transplantation provides recipients with longer survival and better quality of life at a lower cost compared with chronic dialysis. Novel tools are required to assess the quality of the allograft in order to match it to the appropriate recipient and predic graft survival. This project aims to implement novel tests for measuring injury in the kidney and assess their potential impact in clinical practice in an effort to improve both early and late outcomes following kidney transplantation.

描述（由申请人提供）：与慢性透析相比，肾脏移植为接受者提供了更长的生存率和更好的生活质量，成本较低。为了满足对肾脏同种异体移植的需求，正在采购年龄较大和病态的供体的肾脏。这导致了捐赠肾脏的丢弃率更高，并为受体的并发症（包括较短的同种异体移植存活率）提供了更多的并发症。可预测肾脏同种异体移植质量的可用临床模型的预后能力较差，并且不能评估肾脏同种异体损伤的程度。但是，在采购时附近的同种异体移植损伤可能会导致移植受者的重大后果：延迟移植功能的风险更大，同种异体移植功能差和移植的过早丧失。 我们的建议基于以下假设，即采购时在供体尿液和运输培养基中测量的新型肾脏损伤生物标志物可以评估急性和慢性肾脏损伤，并且独特的生物标志物模式可以预测同种异体移植的存活。通过与四个器官采购组织合作，我们将为每个抽水肾脏连续1,000名死者捐赠者和运输解决方案样本收集尿液样品。我们将测量五个急性损伤标记和三个慢性损伤标记。我们将通过连接到联合器官共享（UNOS）数据库来确定所有患者的死亡率和同种异体移植生存。此外，我们将对500多名接受者进行详细的图表审查，还将在移植后两年内检查生物标志物与纵向移植功能之间的关联。 早期，非侵入性和快速评估供体肾脏损伤可以推动更好的分配决策，并有可能降低移植后并发症的率。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脏移植受者的临床试验提供一个平台。 公共卫生相关性：与慢性透析相比，肾脏移植为接受者提供更长的生存率和更高的生活质量。需要新颖的工具 评估同种异体移植物的质量以使其与适当的受体和预性移植物存活相匹配。该项目旨在实施新的测试，以测量肾脏中的损伤，并评估其在临床实践中的潜在影响，以改善肾脏移植后的早期和晚期结果。