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.

抽象的 尽管急性肾损伤 (AKI) 很常见并且与不良后果相关，但没有具体的 AKI 疗法已经出现。这归因于人类 AKI 的异质性，该模型的建模效果不佳 动物实验。肾脏精准医学计划 (KPMP) 由 NIH/NIDDK 在 2016 年研究 AKI 事件期间的人类肾组织，以发现致病途径和新的 治疗目标。约翰·霍普金斯大学 (JHU)/耶鲁大学合并后的网站于第一期获得资助 KPMP 阶段招募 AKI 参与者。在第一阶段，JHU/耶鲁大学网站注册了超过一半的学生 KPMP 的所有 AKI 参与者均以对安全和道德的坚定承诺进行了肾活检， 保留了所有参与者，并通过以下方式在研究方案的启动和执行中发挥了重要作用： 委员会的领导和参与。经过数月的努力，终于成功重启招生 由于 COVID-19 大流行，招募暂停，并制定了监测参与者的方案 和员工安全。这是一份继续作为 Kidney Precision 的 AKI 招募网站的申请 医学计划 (KPMP) 创建高质量、代表性良好的组织和生物样本资源 患有 AKI 的住院参与者。 JHU/耶鲁中心第一阶段研究的经验将是 对于该联盟试图增加第二阶段的入学人数来说，这是无价的。具体目标是： 1) 招募了总共 150 名不同的参与者，他们因不同的病因和不同的严重程度而患有 AKI 研究以安全且合乎道德的方式进行方案研究活组织检查，以收集肾组织并获得 同时的生物样本和临床数据； 2）使用混合方法保留纵向研究的参与者 主动和被动随访，优先考虑参与者的便利性并获得高保真度的随访 信息; 3) 提供来自具有各种活检证实的 AKI 病因的参与者的生物样本 更大的队列和更广泛的入组标准，以从外部验证 KPMP 的研究结果。在目标 1 中，30 个不同的 每年患有 AKI 的参与者将在两个学术医疗中心注册，同时维持。高的 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接近 100% 的随访 收集有关肾脏健康客观指标和患者报告的信息的各种方法 结果。在目标 3 中，为 KPMP 结果、来自 500 多个人的血液、尿液和 DNA 提供外部验证 因 AKI 接受常规临床指示肾活检的参与者将参与该研究。 成功完成这些目标将导致肾组织、生物样本和数据的贡献 具有 AKI 的参与者加入 KPMP 联盟，以帮助实现了解更广泛的目标 人类 AKI 的发病机制。这将导致新的分子靶标和潜在的鉴定 治疗方法以及针对 AKI 患者的更新的诊断工具。