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（阿基）很常见，并伴有不良后果，但没有特异性阿基 治疗已经出现。这归因于人类阿基的异质性，其通过以下方法建模较差： 动物实验。肾脏精准医学计划（KPMP）由NIH/NIDDK于2009年建立。 2016年在阿基事件期间研究人类肾脏组织，以发现致病途径和新的 治疗目标约翰霍普金斯大学/耶鲁大学的合并网站是在第一次资助 KPMP阶段招募阿基参与者。在第一阶段，JHU/Yale研究中心招收了超过一半的学生， 在KPMP的所有阿基参与者中，进行了肾脏活检，并对安全性和伦理学做出了坚定的承诺， 保留所有参与者，并通过以下方式在研究方案的启动和执行中发挥重要作用： 委员会的领导和参与。在长达数月的时间之后， 由于COVID-19大流行而暂停招募，并制定了协议来监测参与者 和员工安全。这是一份继续作为Kidney Precision阿基招募网站的申请 医学计划（KPMP）创建一个高质量的，有代表性的组织和生物样本资源， 阿基住院患者。JHU/耶鲁中心从研究第一阶段获得的经验将是 这是非常宝贵的，因为该联盟试图在第二阶段增加注册人数。具体目标是：（1） 招募了总共150名不同病因和不同严重程度的阿基参与者， 安全且符合伦理的研究，进行方案研究活检，以收集肾组织并获得 同步生物样本和临床数据; 2）使用混合方法保留纵向研究中的参与者 主动和被动随访，优先考虑参与者的便利性，并获得高保真随访 信息;以及3）提供来自具有各种活检证实的阿基病因的参与者的生物样本， 具有更广泛入组标准的更大队列，以外部验证KPMP结果。在目标1中， 每年患有阿基的参与者将在两个学术医疗中心注册，同时保持。高 安全和质量标准。在目标2中，将通过以下方式对研究参与者进行接近100%的随访： 收集肾脏健康客观指标信息的各种方法和患者报告的 结果。在目标3中，为了提供KPMP结果的外部验证，来自500多名 接受常规临床指示的阿基肾活检的参与者将参与本研究。 这些目标的成功完成将导致肾脏组织、生物样品和来自 参与者与阿基的KPMP财团，以帮助实现更广泛的目标，了解 人类阿基的发病机制。这将导致识别新的分子靶点和潜在的 治疗，以及用于阿基患者的新诊断工具。