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（阿基）是一种常见疾病，与短期和长期不良反应相关。 在阿基期间对实际人类肾脏组织的转化研究 事件可以导致发现新的阿基途径和治疗靶点。 作为对RFA-DK-16-026（也称为肾脏精准医学计划）的回应，我们的提案旨在 安全和道德地招募不同的阿基参与者。我们的建议旨在平衡 用于从不同的阿基群体获得肾组织，具有获得该组织的风险。肾脏活检 携带小但显著的出血风险，在阿基的情况下可能会有所增加。 在阿基匹配表型与组织相关的评价（AMPLE-组织）研究中，我们提出， 在阿基患者中获得组织的最佳方式将是通过方法的组合。首先，我们将获得 由于先前的数据表明，这种方法在临床上有指征的肾活检时不需要额外的组织， 不会增加额外的出血风险。我们将仔细选择出血风险较低的参与者。来 在过去的两年里，我们已经招募了200多名参与者参加了一项研究，并收集了来自 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，为了涵盖从最温和到最严重形式的整个阿基谱，我们还将对肾脏进行活检。 在已故的捐赠者身上。死亡供体的阿基原因与危重阿基相似 患者在这种情况下获得活检是低风险的;我们已经成功地招募了900多名死者 在一个正在进行的NIH资助项目中接受肾活检的患者。第三，我们将只进行研究 在肝肾综合征和梗阻性肾病出血时的特殊情况下进行活检 风险低。 在UG 3阶段，我们的目标是在两年内从90-100名参与者中获得活检，并密切监测 患者安全。我们将建立一个阿基患者的社区咨询委员会， 研究的监测委员会。在删除患者标识符后，我们将在联盟内共享数据。我们 还将与各种电子病历系统和行政数据库建立联系 简化后续行动。在UH 3阶段，我们将根据 来自UG 3期的活检质量和安全性数据，并在三年内招募了375名参与者。我们还将 利用对我们有效的各种机制，对所有参与者进行纵向跟踪， 过去