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: 10703455
• 负责人: Chirag R Parikh
• 金额: $ 45万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-12 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10703455
• 关键词: Academic Medical Centers; Acute Renal Failure with Renal Papillary Necrosis; Address; Adverse event; Biological Markers; Biopsy; Blood; COVID-19 pandemic; Cardiovascular system; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Data; Clinical Research; Collaborations; Communities; Critical Care; DNA; Data; Data Linkages; Development; Electronic Health Record; Enrollment; Ensure; Ethics; Ethnic Origin; Etiology; Evaluation; Event; Experimental Animal Model; Funding; Future; Goals; Health; Heterogeneity; Hospital Mortality; Hospitalization; Human; Hybrids; Incidence; Injury to Kidney; Kidney; Kidney Diseases; Leadership; Link; Longitudinal Studies; Measures; Medical; Methods; Molecular; Molecular Target; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Participant; Pathogenesis; Pathogenicity; Pathology; Pathway interactions; Patient Outcomes Assessments; Patient Recruitments; Patients; Persons; Pharmaceutical Preparations; Phase; Phenotype; Physicians; Play; Policies; Primary Care; Privacy; Process; Proteins; Protocols documentation; Race; Radiology Specialty; Research; Research Personnel; Role; Safety; Sampling; Severities; Site; Therapeutic; Tissues; United States National Institutes of Health; Universities; Urine; Validation; Work; adverse outcome; cohort; data quality; data sharing; diagnostic tool; ethnic diversity; experience; follow-up; improved; kidney biopsy; new therapeutic target; novel; novel diagnostics; novel therapeutics; outreach; participant enrollment; participant retention; participant safety; precision medicine; prevent; programs; public health relevance; recruit; remote visit; renal damage; research study; sex; success; tissue resource

Abstract Although acute kidney injury (AKI) is common and associated with adverse consequences, no specific AKI therapy has emerged. This has been attributed to the heterogeneity of human AKI, which is poorly modeled by animal experiments. The Kidney Precision Medicine Program (KPMP) was established by the NIH/NIDDK in 2016 to study human kidney tissue during an AKI event in order to discover pathogenic pathways and novel therapeutic targets. The combined Johns Hopkins University (JHU)/Yale University site was funded in the first phase of the KPMP to recruit AKI participants. During this first phase, the JHU/Yale site enrolled over one-half of all AKI participants in KPMP, performed kidney biopsies with a strong commitment to safety and ethics, retained all participants, and played an important role in the initiation and execution of study protocols through committee leadership and participation. Enrollment was successfully restarted after a several-months-long pause in recruitment due to the COVID-19 pandemic, and protocols were established to monitor participant and staff safety. This is an application to continue to serve as an AKI recruitment site for the Kidney Precision Medicine Program (KPMP) to create a high-quality, well-represented resource of tissues and biosamples from hospitalized participants with AKI. The JHU/Yale center’s experience from the first phase of the study will be invaluable as the consortium attempts to increase enrollment in the second phase. The specific aims are: 1) To recruit a total of 150 diverse participants with AKI due to various etiologies and of varying severities in a research study that safely and ethically performs protocol research biopsies to collect kidney tissue and obtain concurrent biosamples and clinical data; 2) to retain participants in a longitudinal study using a hybrid approach of active and passive follow-up that prioritizes participant convenience and obtains high-fidelity follow-up information; and 3) to contribute biosamples from participants with various biopsy-proven etiologies of AKI from larger cohorts with broader enrollment criteria to externally validate KPMP findings. In Aim 1, 30 diverse participants with AKI per year will be enrolled across two academic medical centers while maintaining. high safety and quality standards. In Aim 2, close to 100% follow-up of study participants will be obtained through various approaches to garner information on objective measures of kidney health and patient-reported outcomes. In Aim 3, to provide external validation of the KPMP findings, blood, urine, and DNA from over 500 participants who underwent routine clinically-indicated kidney biopsies for AKI will be contributed to the study. Successful completion of these aims will result in the contribution of kidney tissue, biosamples, and data from participants with AKI to the KPMP consortium to help achieve the broader goal of understanding the pathogenesis of human AKI. This will lead to the identification of novel molecular targets and potential therapies, as well as newer diagnostic tools for patients with AKI.

摘要 虽然急性肾损伤(AKI)很常见，并与不良后果相关，但没有特殊的AKI 治疗方法已经出现。这归因于人类AKI的异质性，这一点没有得到很好的建模 动物实验。肾脏精准医学计划(KPMP)是由NIH/NIDDK于#年建立的 2016在AKI事件期间研究人类肾脏组织，以发现致病途径和新的 治疗靶点。约翰霍普金斯大学(JHU)和耶鲁大学合并后的网站在第一个月获得了资金 KPMP阶段招募AKI参与者。在第一阶段，JHU/Yale网站招收了超过一半的学生 在KPMP的所有AKI参与者中，他们以对安全和道德的坚定承诺进行了肾脏活检， 保留了所有参与者，并通过以下方式在启动和执行研究方案方面发挥了重要作用 委员会的领导和参与。在几个月的时间后，注册成功重新开始 由于新冠肺炎疫情，暂停招募，并制定了监测参与者的协议 和员工安全。这是一份申请，希望继续担任肾脏精密公司的AKI招聘网站 医学计划(KPMP)，以创建高质量、具有良好代表性的组织和生物样本资源 因AKI住院的参与者。JHU/耶鲁中心第一阶段研究的经验将是 由于财团试图在第二阶段增加招生人数，这是非常宝贵的。具体目标是：1) 招募150名因各种病因和不同严重程度的AKI的不同参与者 安全和合乎道德地进行方案研究活组织检查以收集肾组织并获得 并行生物样本和临床数据；2)使用混合方法留住纵向研究的参与者 主动和被动的跟进，优先考虑参与者的便利性并获得高保真的跟进 信息；以及3)提供具有各种活检证实的AKI病因的参与者的生物样本 具有更广泛的登记标准的更大的队列，以外部验证KPMP的调查结果。在目标1中，30个不同 每年AKI的参与者将在两个学术医疗中心登记，同时保持。高 安全和质量标准。在目标2中，将通过以下方式获得研究参与者近100%的随访 获取有关肾脏健康和患者报告的客观指标的信息的各种方法 结果。在目标3中，提供对KPMP结果、血液、尿液和来自500多个人的DNA的外部验证 因AKI而接受常规临床指征肾脏活检的参与者将参与这项研究。 这些目标的成功完成将导致肾组织、生物样本和来自 KPMP财团的AKI参与者将帮助实现更广泛的目标，即了解 人类AKI的发病机制。这将导致识别新的分子目标和潜力 治疗方法，以及为AKI患者提供的较新诊断工具。