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: 9233645
• 负责人: Chirag R Parikh
• 金额: $ 70.58万
• 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 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9233645
• 关键词: Acute; Acute Kidney Tubular Necrosis; Acute Renal Failure with Renal Papillary Necrosis; Affect; Age-Years; Allografting; Antibody Formation; Asses; Bayesian Modeling; Biological; Biological Markers; Biological Process; Biopsy; Cessation of life; Chronic; Clinical; Collaborations; Coupled; Creatinine; Data; Databases; Development; Dialysis procedure; Early treatment; End stage renal failure; Enrollment; Event; Functional disorder; Grant; Immunosuppression; Individual; Inflammation; Inflammatory Response; Injury; Interleukin-18; Ischemia; Kidney; Kidney Transplantation; LCN2 gene; Lead; Link; Measures; Methods; Modeling; Natural History; Organ Donations; Organ Procurements; Organ Transplantation; Outcome; Pathway interactions; Patients; Pattern; Perioperative; Phase; Population; Publishing; Pump; Quality of life; Recovery; Recruitment Activity; Renal function; Resources; Risk; Safety; Sampling; Science; Serum; Staging; Statistical Methods; Techniques; Testing; Therapeutic Trials; Time; Transplant Recipients; Transplantation; United Network for Organ Sharing; Urine; Waiting Lists; base; biobank; biomarker panel; clinical practice; cohort; cost; delayed graft function; follow-up; genetic regulatory protein; graft failure; graft function; high risk; improved; innovation; insight; isoimmunity; kidney allograft; meetings; mortality; novel; novel marker; organ procurement transplantation network; parent grant; phase 1 study; phase 2 study; premature; prognostic; protective effect; protein biomarkers; rat KIM-1 protein; repaired; secondary outcome; survival prediction; tool; trend; urinary

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.

项目摘要 与慢性透析相比，肾移植为受者提供了更好的存活率 和生活质量，而成本要低得多。为满足日益增长的需求所做的努力产生了更多 从年长和病情较重的捐赠者那里获取肾脏。不幸的是，这些努力导致了 获取的肾脏的丢弃率更高，同种异体移植接受者的并发症更多， 包括同种异体移植功能降低。现有的预测同种异体移植物质量的工具很差 预后能力，不能充分评估肾脏损伤的程度或修复潜力 采购部。然而，早期的同种异体移植损伤可能会导致受者的严重后果， 如移植物功能延迟、长期同种异体移植物功能差和过早发生的风险更大 移植手术的损失。 我们的建议是基于这样的假设：新的损伤、炎症和 在采购时在供者尿液和运输介质中测量的修复将确定 预测同种异体移植物存活的独特且信息丰富的模式。与五个人合作 对于器官采购组织的第一阶段研究，我们收集了来自 超过1500名连续的已故捐赠者和灌流液样本来自每个被泵送的肾脏和 测量了几个肾脏损伤的生物标志物。我们链接了来自这些捐赠者的所有收件人(完 2500人)在器官共享联合网络(UNOS)数据库中确定 死亡率和同种异体移植存活率。在第二阶段，我们将测量17个有前途的新生物标记物 我们的生物库样本代表了各种生物过程。我们将扩大 收件人子队列将包括1000多名收件人，以丰富重要的事件发生率 免疫学结果(即急性排斥和渐进性同种异体免疫)，并收集详细的 UP患者同种异体移植功能、免疫抑制和特殊并发症的纵向数据 通过详细的图表回顾，移植后至5年。总共测量了超过25个 生物标志物、更多的临床事件、更长的随访时间和创新的统计方法，我们 将创建多标记小组来评估捐赠者肾脏的质量并预测关键结果。 对捐赠者生物过程的早期、非侵入性和快速评估可以更好地推动 分配决策和减少移植后并发症。这些新工具还可以 为肾移植和受者的治疗试验提供一个平台，旨在改善 损伤，促进恢复，并改善长期同种异体移植的功能和存活率。