AKI Matched Phenotype Linked Evaluation with Tissue (AMPLE-Tissue)

AKI 匹配表型相关组织评估 (AMPLE-Tissue)

• 批准号: 9911045
• 负责人: Chirag R Parikh
• 金额: $ 30万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9911045
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Animal Model; Animals; Biopsy; Brain Death; Cessation of life; Clinical; Clinical Trials; Clinical Trials Data Monitoring Committees; Collection; Communities; Complex; Computerized Medical Record; Consent; Core Biopsy; Critical Illness; Data; Data Linkages; Data Quality; Dialysis procedure; Enrollment; Equilibrium; Ethics; Etiology; Evaluation; Event; Excision; Family; Funding; Health Care Costs; Hemorrhage; Hepatorenal Syndrome; Histologic; Hospitalization; Human; Human Characteristics; Incidence; Intensive Care Units; Intervention; Kidney; Kidney Diseases; Kidney Transplantation; Lead; Link; Living Donors; Longterm Follow-up; Medical; Medical Records; Molecular; Molecular Target; Monitor; Morbidity - disease rate; Nephrectomy; Participant; Pathology; Pathway interactions; Patient Monitoring; Patients; Percutaneous Nephrostomy; Persons; Phase; Phenotype; Population; Prospective Studies; Renal Cell Carcinoma; Renal function; Reproducibility; Research; Risk; Risk Factors; Safety; Sampling; Selection Bias; Severities; Site; System; Telephone; Time; Tissues; Transfusion; Translational Research; United States National Institutes of Health; Visit; administrative database; adverse outcome; base; clinically significant; cohort; cost; data sharing; electronic data; endophenotype; experience; follow-up; human disease; human tissue; kidney biopsy; liver transplantation; mortality; novel; novel marker; patient safety; precision medicine; programs; public health relevance; recruit; research study; response; specific biomarkers; targeted treatment; therapeutic target; urinary tract obstruction

Abstract Acute kidney injury (AKI) is a common condition and is associated with both short- and long-term adverse outcomes in those who develop it. Translational research studies of actual human kidney tissue during an AKI event can lead to discovery of novel AKI pathways and therapeutic targets. In response to the RFA-DK-16-026, also known as the Kidney Precision Medicine Program, our proposal aims to safely and ethically enroll a diverse group of participants with AKI. Our proposal aims to balance the need for obtaining kidney tissue from a diverse AKI population with the risks of obtaining this tissue. Kidney biopsies carry a small but significant risk of bleeding which may be somewhat increased in the setting of AKI. In the AKI Matched Phenotype Linked Evaluation with Tissue (AMPLE-Tissue) Study, we propose that the optimal way to obtain tissue in AKI patients would be through a combination of approaches. First, we will obtain extra tissue at the time of clinically indicated kidney biopsies, since prior data suggests that this approach does not add additional bleeding risk. We will carefully select participants who are at lower risk of bleeding. Over the last two years, we have enrolled over 200 participants in a research study and collected kidney biopsies from them. Over 70% of these participants said that they would be willing to donate extra tissue for research. Second, to encompass the whole AKI spectrum from its mildest to severest forms, we will also biopsy kidneys in deceased donors. The causes of AKI in deceased donors are similar to those experienced by critically ill AKI patients. Obtaining biopsies in this setting is low-risk; we have successfully enrolled over 900 deceased patients who received kidney biopsies in an ongoing NIH-funded project. Third, we will obtain research-only biopsies in specially-selected settings of hepatorenal syndrome and obstructive kidney disease when bleeding risk is low. In the UG3 phase, our aim is to obtain biopsies from 90-100 participants over two years and closely monitor patient safety. We will establish a community advisory board of AKI patients in addition to a data and safety monitoring board for the study. We will share data within the consortium after removal of patient identifiers. We will also establish linkages with various electronic medical record system as well as administrative databases to streamline follow-up. In the UH3 phase, we will expand our study to other sites and settings based on the biopsy quality and safety data from UG3 phase and enroll 375 participants over three years. We will also conduct longitudinal follow-up on all participants using various mechanisms which were effective for us in the past.

抽象的 急性肾脏损伤（AKI）是一种常见状况，与短期和长期不利有关 那些发展它的人的结果。 AKI期间实际人类肾组织的翻译研究 事件可能导致发现新颖的AKI途径和治疗靶标。 为了响应RFA-DK-16-026，也称为肾脏精密医学计划，我们的提案目标 安全地和道德地招募AKI的一群参与者。我们的建议旨在平衡需求 从不同的AKI种群中获得肾脏组织，并有获得该组织的风险。肾脏活检 出现小而显着的出血风险，在AKI的情况下可能会有所增加。 在AKI匹配的表型与组织（Ample-Tissue）研究相关的表型中，我们建议 在AKI患者中获得组织的最佳方法将是通过方法组合。首先，我们将获得 在临床表明肾脏活检时的额外组织，因为先前的数据表明这种方法确实 不要增加其他出血风险。我们将仔细选择患有较低流血风险的参与者。在 最近两年，我们已经招募了200多名参与者参加了一项研究，并从 他们。超过70％的参与者表示，他们愿意捐赠额外的组织进行研究。 其次，要从最轻度到最严重的形式涵盖整个AKI频谱，我们还将活检肾脏 在已故的捐助者中。死者捐助者中AKI的原因与危重病的捐赠者相似 患者。在这种情况下获得活检是低风险的；我们已经成功招募了900多名死者 在正在进行的NIH资助项目中接受肾脏活检的患者。第三，我们将获得仅研究的 出血时，在特殊选择的肝烯醇综合征和阻塞性肾脏疾病的活检中 风险很低。 在UG3阶段，我们的目标是在两年内从90-100名参与者中获得活检，并密切监视 患者安全。除了数据和安全性外，我们还将成立一个AKI患者的社区顾问委员会 研究委员会的监测委员会。删除患者标识符后，我们将在财团内共享数据。我们 还将与各种电子病历系统以及行政数据库建立联系 简化后续行动。在UH3阶段，我们将根据 UG3阶段的活检质量和安全数据在三年内招募了375名参与者。我们也会 对所有参与者进行纵向随访，使用对我们有效的各种机制 过去的。