The KIDCOV Study: Assessment of Kidney Injury and Associated Risk Factors for SARS-CoV-2

KIDCOV 研究：评估 SARS-CoV-2 肾损伤及相关风险因素

• 批准号: 10216618
• 负责人: Jochen Reiser
• 金额: $ 45.96万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10216618
• 关键词: 2019-nCoV; Academic Medical Centers; Acute; Acute Kidney Failure; Acute Renal Failure with Renal Papillary Necrosis; Address; African American; Alaska Native; American Indians; Asians; Asses; Back; Biological Assay; Biological Markers; Blood Tests; COVID-19; COVID-19 pandemic; CXCL10 gene; California; Cells; Clinical; Cohort Studies; Collection; Communities; Computerized Medical Record; Consent; Creatinine; Custom; DNA; DNA Methylation; Data; Data Analyses; Data Coordinating Center; Demographic Factors; Detection; Diagnosis; Disease; Electronic Health Record; Enrollment; Ethnic Origin; Evolution; Focal Segmental Glomerulosclerosis; Geography; Health Status; High Prevalence; Home environment; Human; Illinois; Incidence; Individual; Infection; Injury to Kidney; Island; Kidney; Kidney Diseases; LCN2 gene; Low Prevalence; Michigan; Minority; Multicenter Studies; Native Hawaiian; Needles; Outpatients; Parents; Participant; Patients; Peptidyl-Dipeptidase A; Phase; Population; Population Density; Prevalence; Prospective Studies; Prospective cohort; Proteins; Proteinuria; Publishing; Questionnaires; Race; Recording of previous events; Renal tubule structure; Reporting; Research; Research Design; Risk; Risk Factors; Running; Sampling; Serum; Ships; Site; Social Distance; Specific qualifier value; Sterility; Symptoms; Telephone; Temperature; Test Result; Testing; Time; Tissues; Universities; Urine; Variant; Virus; Virus Diseases; base; cell free DNA; cohort; comorbidity; coronavirus disease; cytokine release syndrome; demographics; epidemiologic data; ethnic diversity; follow-up; high risk; infection risk; innovative technologies; novel; prospective; receptor; renal damage; screening; standard of care; sulfated glycoprotein 2; urinary; viral RNA

ABSTRACT From early studies and published reports indicate kidney injury is one of the manifestations of COVID-19. The human kidney is a direct target of the virus, as the angiotensin-converting enzyme 2 (ACE2), a putative receptor for SARS-CoV-2, is highly expressed in the kidney tubules. As direct evidence of the virus localizing to the kidney, SARS-CoV-2 viral RNA can be observed in urine and kidney tissue from patients with COVID-19. Kidney injury can result in acute kidney injury in ~60% of hospitalized patients. The incidence, prevalence and risk factors of kidney injury in patients with mild/ asymptomatic out-patient COVID-19 disease is as yet unknown. This forms a large cohort of SARS-CoV-2 infected patients in the community world-wide. We propose in this supplement to the parent RO1 that examines suPAR and other circulating factors in FSGS disease, that urinary suPAR and other urine biomarkers that comprise a novel highly sensitive and quantitative assay (the Kidney Injury Test), can provide an assessment of the incidence and prevalence of kidney damage in COVID-19 by home-based urine testing, independent of any blood test requirement. In this study, we are hypothesizing that risk of kidney injury in COVID-19 disease, also varies by race/ethnicity and other demographic factors, is exacerbated by COVID-19 infection, and is more severe in those with a history of or risk factors of kidney disease. We have made careful selection of 7 large academic medical center study sites, in 3 states, to address these questions in the KIDCOV prospective, multi-center study. To test the hypothesis and to achieve the aim of the KIDCOV project, we will perform the study in three stages:. In the first stage, we will enroll outpatient COVID-19 positive patients. COVID-19 positive patients will be enrolled from academic medical centers in California (University of California, 5 campuses), Michigan (University of Michigan) and Illinois (Rush University). Prospective matched cohorts of COVID positive and COVID negative individuals, balanced by race/ethnicity, will be identified through EMRs and contacted by phone within 2 weeks of screening to provide consent and complete a baseline questionnaire. In the second stage, over the following 12 months, urine samples will be collected and shipped for the assessment of specific urinary markers at UCSF central lab (cell-free DNA (cfDNA), methylation of cell-free DNA (mcf-DNA), clusterin, CXCL10, protein and creatinine) to compute a validated Kidney Injury Test (KIT)-Score for sensitive assessment of early kidney damage. Acute kidney injury markers, NGAL, KIM-1 and suPAR will also be quantitated in urine as correlates of kidney damage with the KIT-Score. In the final phase, data analysis will be done to compare the proportion of patients with kidney injury between the COVID-19 positive and COVID-19 negative groups and identify groups at higher risk for kidney injury, with primary focus on COVID19 status, history/risk factors of prior kidney disease, and geographic, demographic and ethnic variation.

抽象的 早期研究和已发表的报告表明肾损伤是 COVID-19 的表现之一。这 人类肾脏是该病毒的直接目标，因为血管紧张素转换酶 2 (ACE2) 是一种假定的受体 SARS-CoV-2 在肾小管中高表达。作为病毒定位于肾脏的直接证据， 在 COVID-19 患者的尿液和肾组织中可以观察到 SARS-CoV-2 病毒 RNA。肾脏损伤 可导致约 60% 的住院患者出现急性肾损伤。发病率、患病率和危险因素 轻度/无症状门诊 COVID-19 患者肾损伤的影响尚不清楚。这 在世界各地的社区中形成了一大群 SARS-CoV-2 感染患者。 我们建议在对父 RO1 的补充中检查 FSGS 中的 suPAR 和其他循环因子 疾病，尿液suPAR和其他尿液生物标志物包含一种新型的高度敏感和定量的 测定（肾损伤测试），可以评估肾损伤的发生率和患病率 通过家庭尿液检测来检测 COVID-19，独立于任何血液检测要求。在这项研究中，我们 假设 COVID-19 疾病中肾损伤的风险也因种族/民族和其他因素而异 人口因素，因 COVID-19 感染而加剧，并且在有感染史或有感染风险的人中更为严重 肾脏疾病的因素。我们精心挑选了 7 个大型学术医学中心研究地点， 3 个州，通过 KIDCOV 前瞻性、多中心研究来解决这些问题。 为了检验假设并实现 KIDCOV 项目的目标，我们将分三个阶段进行研究： 在第一阶段，我们将招募门诊 COVID-19 阳性患者。将招募 COVID-19 阳性患者 来自加州（加州大学，5 个校区）、密歇根州（加州大学）的学术医疗中心 密歇根州）和伊利诺伊州（拉什大学）。新冠病毒阳性和新冠病毒阴性的预期匹配队列 按种族/族裔平衡的个人将通过电子病历进行识别，并在两周内通过电话联系 筛选以提供同意并完成基线调查问卷。 第二阶段，在接下来的12个月内，将收集并运送尿液样本进行评估 UCSF 中心实验室的特定尿液标记物（游离 DNA (cfDNA)、游离 DNA 甲基化 (mcf-DNA)、 clusterin、CXCL10、蛋白质和肌酐）来计算经过验证的肾损伤测试 (KIT) - 敏感的评分 评估早期肾损伤。急性肾损伤标志物 NGAL、KIM-1 和 suPAR 也将被纳入 在尿液中进行定量，作为肾脏损伤与 KIT 评分的相关性。 在最后阶段，将进行数据分析，比较不同国家之间肾损伤患者的比例。 COVID-19 阳性和 COVID-19 阴性群体，并确定肾损伤风险较高的群体，其中原发性 重点关注新冠肺炎 (COVID19) 状况、既往肾脏疾病史/危险因素以及地理、人口和种族 变化。