Novel Kidney Injury Tools in Deceased Organ Donation to Predict Graft Outcomes

死亡器官捐赠中预测移植结果的新型肾损伤工具

• 批准号: 10177020
• 负责人: Chirag R Parikh
• 金额: $ 71.8万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10177020
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Affect; Atlases; Biological; Biological Markers; Biopsy; Blood; Blood specimen; CCL2 gene; COVID-19; COVID-19 pandemic; Cells; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Management; Clinical Trials; Communities; Coronavirus; Country; Data; Dialysis procedure; Disease; Disease Outcome; Disease Pathway; Ensure; Evaluation; Event; Funding; Grant; Guidelines; Hospitalization; Hospitals; Human; IL7 gene; Incidence; Infection; Inflammation; Injury; Injury to Kidney; Interleukin-10; Interleukin-2; Kidney; Kidney Diseases; Lead; Longterm Follow-up; Lung diseases; Medical Research; Medicine; Middle East Respiratory Syndrome; Myocarditis; Observational Study; Organ; Organ Donations; Outcome; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Peptidyl-Dipeptidase A; Pharmacotherapy; Phenotype; Plasma; Productivity; Proteinuria; Recording of previous events; Renal function; Reporting; Research; Research Personnel; Respiratory System; Risk Factors; Role; SARS coronavirus; Sampling; Secondary to; Severe Acute Respiratory Syndrome; Severities; Severity of illness; Small Nuclear RNA; Survivors; TNF gene; Therapeutic; Tissue Sample; Translational Research; Tubular formation; United States; United States National Institutes of Health; Urine; Viral; Virus; Virus Diseases; Work; acute liver injury; clinical development; clinical predictors; cohort; combat; coronavirus disease; epidemiology study; experience; follow-up; improved; insight; interdisciplinary approach; kidney biopsy; mortality; multidisciplinary; new therapeutic target; novel; pandemic disease; podocyte; prognostic value; prospective; receptor; repaired; research study; single-cell RNA sequencing; tool; transcriptomics

Abstract The incidence of AKI is 20-30% in patients hospitalized with COVID-19 in the United States, and is over 40% in patients admitted to the ICU. Moreover, the mortality rate in patients that experience AKI in the setting of COVID-19 is approximately 2- to 10-fold higher than patients without AKI. The pathogenesis of AKI in COVID-19 infection remains unclear and it is not known if the injury to the tubule is direct result of the virus infection or if it is secondary to other organ complications. Availability of urine, blood and tissue samples early in the course of infection will provide important pathogenic insights for therapeutic and clinical management. The Translational Research investigating Biomarker Endpoints (TRIBE)-AKI consortium has a long-standing history of conducting multidisciplinary epidemiologic and translational research studies in the setting of AKI. They have experience with long term follow-up of hospitalized patients, tissue and sample handling as well as analytic considerations. We propose a prospective observational study of the clinical and biologic predictors of major adverse kidney events and death (MAKE-D) in COVID-19, including the following: severity of AKI (stages 1, 2, 3 and requiring dialysis), mortality, and non-recovery of AKI and transition to chronic kidney disease. We will examine consecutive patients hospitalized with COVID-19 at three premier academic hospitals participating in the TRIBE consortium: Johns Hopkins Medicine, Mount Sinai Hospital and Yale-New Haven Hospital. We assess the incidence, severity, and clinical predictors of MAKE-D during hospitalization and at 90 days following discharge. We will investigate the possible role of injury, inflammation and repair mechanisms through biomarkers in the blood and urine in serial samples collected from patients during hospitalization. We will also perform advanced evaluation of kidney biopsies using single cell RNA sequencing to identify possible mechanistic disease pathways, which may lead to novel therapeutic targets. Combating this pandemic will require a multidisciplinary approach from the medical research community, including rigorously conducted epidemiologic studies that include granular patient- level data and translational research studies to understand the pathogenesis of COVID- associated kidney disease.

抽象的 在美国住院的患者中，AKI的发病率为20-30％，在美国， 入学ICU患者的40％以上。此外，患者的死亡率 AKI在Covid-19的环境中的体验比患者高约2至10倍 没有Aki。 Covid-19感染中AKI的发病机理尚不清楚，尚不清楚 如果小管的损伤是病毒感染的直接结果，或者是其他器官的次要的 并发症。感染过程中早期的尿液，血液和组织样品的可用性将 为治疗和临床管理提供重要的致病见解。 调查生物标志物端点（部落） - 阿基联盟的转化研究 进行多学科流行病学和转化研究的长期历史 在AKI环境中的研究。他们有长期随访的经验 患者，组织和样品处理以及分析考虑。我们提出了一个 主要不良肾脏的临床和生物学预测因子的前瞻性观察性研究 COVID-19的事件和死亡（Make-D），包括以下内容：AKI的严重性（第1、2阶段， 3并且需要透析），死亡率和未恢复AKI并过渡到慢性肾脏 疾病。 我们将检查连续的患者在三个高级学术学业上住院的COVID-19 参加部落财团的医院：西奈山医院的约翰·霍普金斯医学 和耶鲁新避风港医院。我们评估 在住院期间和出院后的90天后进行D。我们将调查 通过血液中生物标志物的损伤，炎症和修复机制的可能作用 在住院期间从患者那里收集的连续样品中的尿液和尿液。我们也会表演 使用单细胞RNA测序对肾脏活检的高级评估以识别可能 机械疾病途径，这可能导致新的治疗靶标。 打击这个大流行将需要医学研究的多学科方法 社区，包括严格进行的流行病学研究，包括颗粒状患者 水平数据和翻译研究，以了解共证的发病机理 相关的肾脏疾病。