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: 10493566
• 负责人: Chirag R Parikh
• 金额: $ 55万
• 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/10493566
• 关键词: Academic Medical Centers; Acute Renal Failure with Renal Papillary Necrosis; Address; Adverse event; Animal Experiments; 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; Etiology; Evaluation; Event; Follow-Up Studies; Funding; Future; Goals; Health; Heterogeneity; Hospitalization; Hospitals; Human; Hybrids; Injury to Kidney; Kidney; Kidney Diseases; Leadership; Link; Longitudinal Studies; Measures; Medical; Methods; Modeling; 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 Health Care; Privacy; Process; Proteins; Protocols documentation; Radiology Specialty; Research; Research Personnel; Role; Safety; Sampling; Severities; Site; Therapeutic; Time; 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; racial and ethnic; 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.

抽象的 尽管急性肾脏损伤（AKI）很常见，并且与不利后果有关，但没有特定的AKI 疗法已经出现。这归因于人类AKI的异质性，该异质性的建模不佳 动物实验。 NIH/NIDDK建立了肾脏精密医学计划（KPMP） 2016年在AKI事件中研究人类肾脏组织，以发现致病途径和新颖 治疗靶标。约翰·霍普金斯大学（JHU）联合的耶鲁大学网站是在第一个资金的 毕马威（KPMP）招募AKI参与者的阶段。在第一阶段，JHU/YALE网站占了一半以上 在毕马威（KPMP）的所有AKI参与者中，都进行了肾脏活检，并致力于安全和道德， 保留所有参与者，并通过 委员会的领导和参与。长达几个月后，入学率成功重新开始 由于19日大流行而招募招募，并建立了协议以监视参与者 和员工安全。这是继续作为肾脏精确度的AKI招聘网站的申请 医学计划（KPMP）创建来自组织和生物样本的高质量，代表性良好的资源 住院的参与者AKI。从研究的第一阶段开始，JHU/耶鲁中心的经验将是 随着财团试图在第二阶段增加入学人数，无价。具体目的是：1） 由于各种病因和在 安全和道德上执行协议活检的研究研究，以收集肾脏组织并获得 并发生物样本和临床数据； 2）使用混合方法保留参与者参加纵向研究 主动和被动的随访，优先考虑参与方便并获得高保真随访 信息; 3）从AKI的各种活检证实病因的参与者中贡献生物样本。 较大的人群具有更广泛的入学标准，可在外部验证毕马威的发现。在AIM 1，30名潜水员 每年有AKI的参与者将在维护的同时在两个学术医疗中心招收。高的 安全和质量标准。在AIM 2中，将通过接近100％的研究参与者随访 各种方法来获得有关肾脏健康和患者报告的客观措施的信息 结果。在AIM 3中，为了提供毕马威点的外部验证，血液，尿液和DNA超过500 对AKI进行常规临床指示的肾脏活检的参与者将为这项研究做出贡献。 这些目标的成功完成将导致肾脏组织，生物样本和数据的贡献 毕马威会议财团的AKI参与者，以帮助实现更广泛的目标 人AKI的发病机理。这将导致鉴定新的分子靶标和电势 为AKI患者的疗法以及更新的诊断工具。