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: 10225441
• 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/10225441
• 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; 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.

抽象的 急性肾损伤 (AKI) 是一种常见病症，与短期和长期不良反应相关 开发它的人的成果。 AKI 期间实际人体肾组织的转化研究 事件可以导致新的 AKI 途径和治疗靶点的发现。 为了响应 RFA-DK-16-026（也称为肾脏精准医学计划），我们的提案旨在 安全、合乎道德地招募 AKI 的多元化参与者。我们的建议旨在平衡需求 用于从不同的 AKI 人群中获取肾组织，但存在获取该组织的风险。肾脏活检 具有较小但显着的出血风险，在 AKI 情况下可能会有所增加。 在 AKI 匹配表型相关组织评估 (AMPLE-Tissue) 研究中，我们建议 为 AKI 患者获取组织的最佳方法是通过多种方法的组合。首先，我们将获得 在临床指示的肾活检时进行额外的组织，因为先前的数据表明这种方法确实 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。超过 过去两年，我们招募了 200 多名参与者参加一项研究，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，为了涵盖从最轻微到最严重形式的整个 AKI 谱系，我们还将对肾脏进行活检 在已故的捐赠者中。已故捐献者发生 AKI 的原因与危重 AKI 的原因相似 患者。在这种情况下进行活检的风险较低；我们已成功登记了 900 多名死者 在 NIH 资助的正在进行的项目中接受肾活检的患者。第三，我们将获得仅供研究的 在肝肾综合征和阻塞性肾病出血时特殊选择的情况下进行活检 风险低。 在 UG3 阶段，我们的目标是在两年内对 90-100 名参与者进行活检并密切监测 患者安全。除了数据和安全委员会之外，我们还将建立 AKI 患者社区咨询委员会 该研究的监督委员会。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以及行政数据库建立联系 以简化后续工作。在UH3阶段，我们将根据以下情况将研究扩展到其他地点和环境 UG3 阶段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 使用对我们有效的各种机制对所有参与者进行纵向跟踪 过去的。

项目成果

Effects of the SGLT2 inhibitor canagliflozin on plasma biomarkers TNFR-1, TNFR-2 and KIM-1 in the CANVAS trial.

• DOI: 10.1007/s00125-021-05512-5
• 发表时间: 2021-10
• 期刊: Diabetologia
• 影响因子: 8.2
• 作者: Sen T;Li J;Neuen BL;Neal B;Arnott C;Parikh CR;Coca SG;Perkovic V;Mahaffey KW;Yavin Y;Rosenthal N;Hansen MK;Heerspink HJL
• 通讯作者: Heerspink HJL

Biomarkers of Acute and Chronic Kidney Disease.

• DOI: 10.1146/annurev-physiol-020518-114605
• 发表时间: 2019-02-10
• 期刊: Annual review of physiology
• 影响因子: 18.2
• 作者: Zhang WR;Parikh CR
• 通讯作者: Parikh CR

Genome-wide Association Study for AKI.

• DOI: 10.34067/kid.0000000000000175
• 发表时间: 2023-07-01
• 期刊: Kidney360
• 作者: Bhatraju PK;Stanaway IB;Palmer MR;Menon R;Schaub JA;Menez S;Srivastava A;Wilson FP;Kiryluk K;Palevsky PM;Naik AS;Sakr SS;Jarvik GP;Parikh CR;Ware LB;Ikizler TA;Siew ED;Chinchilli VM;Coca SG;Garg AX;Go AS;Kaufman JS;Kimmel PL;Himmelfarb J;Wurfel MM
• 通讯作者: Wurfel MM