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.

摘要 急性肾损伤(AKI)是一种常见的疾病，与短期和长期的不良反应有关。 结果发生在那些发展它的人身上。急性肾移植中人肾组织的翻译研究 事件可以导致新的AKI途径和治疗靶点的发现。 为了响应RFA-DK-16-026，也被称为肾脏精准医学计划，我们的提案旨在 以安全和合乎道德的方式为不同群体的参与者注册AKI。我们的建议旨在平衡这一需求 从有获取肾组织风险的不同AKI人群中获取肾组织。肾活检 有少量但严重的出血风险，在AKI的情况下可能会有所增加。 在AKI匹配表型评估与组织(充分组织)研究中，我们建议 获取AKI患者组织的最佳方法是通过多种方法的组合。首先，我们将获得 临床指征的肾脏活检时的额外组织，因为先前的数据表明这种方法有 不会增加额外的出血风险。我们将仔细挑选出血风险较低的参与者。超过了 在过去的两年里，我们招募了200多名参与者参加一项研究，并从 他们。超过70%的参与者表示，他们愿意捐赠额外的组织用于研究。 其次，为了涵盖从最轻到最重的AKI的整个谱系，我们还将对肾脏进行活检 在已故捐赠者身上。已故供者发生急性KI的原因与病情危重的AKI相似。 病人。在这种情况下获得活组织检查的风险很低；我们已经成功地招募了900多名死者 在NIH资助的一个正在进行的项目中接受肾脏活检的患者。第三，我们将只获取研究报告 肝肾综合征和梗阻性肾病出血时的特殊情况下的活检 风险很低。 在UG3阶段，我们的目标是在两年内从90-100名参与者那里获得活组织检查，并密切监测 病人安全。除了数据和安全，我们还将建立一个AKI患者的社区咨询委员会 这项研究的监督委员会。删除患者身份标识后，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 以简化后续工作。在UH3阶段，我们会将研究扩展至其他地点和环境，以 来自UG3阶段的活检质量和安全数据，并在三年内招募了375名参与者。我们还将 使用各种机制对所有参与者进行纵向跟踪，这些机制对我们在 过去时。