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

摘要 早期研究和已发表的报告表明，肾损伤是COVID-19的表现之一。的 人肾脏是病毒的直接靶点，因为血管紧张素转换酶2（ACE2）是一种假定的受体 SARS-CoV-2在肾小管中高度表达。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。肾损伤 可导致约60%的住院患者发生急性肾损伤。发病率、患病率和危险因素 目前尚不清楚轻度/无症状门诊COVID-19疾病患者的肾损伤情况。这 在世界范围内的社区中形成了一个大的SARS-CoV-2感染患者队列。 我们建议在本补充的父RO 1，检查suPAR和其他循环因子在FSGS 疾病、尿suPAR和其它尿生物标志物，其包括新高度敏感和定量的 肾损伤试验（Kidney Injury Test）可以评估肾损伤的发生率和患病率 在COVID-19通过家庭尿液检测，独立于任何血液检测要求。本研究 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感染而加重，在有COVID-19病史或风险的人群中更为严重 肾脏疾病的因素。我们精心挑选了7个大型学术医疗中心的研究地点， 在KIDCOV前瞻性多中心研究中解决这些问题。 为了验证假设并实现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。COVID-19阳性患者将入组 来自加州（加州大学，5个校区）、密歇根大学（密歇根大学， 密歇根州）和伊利诺伊州（拉什大学）。COVID阳性和COVID阴性的前瞻性匹配队列 将通过EMR识别受试者（按种族/民族平衡），并在2周内通过电话联系 筛选以提供知情同意并完成基线问卷。 在第二阶段，在接下来的12个月内，将收集并运送尿液样本进行评估 在UCSF中心实验室的特定尿液标志物（无细胞DNA（cfDNA），无细胞DNA的甲基化（mcf-DNA）， clusterin、CXCL10、蛋白质和肌酸酐）来计算经验证的肾损伤测试（KIT）-敏感性肾损伤的评分。 评估早期肾损伤。急性肾损伤标志物NGAL、KIM-1和suPAR也将被检测。 在尿中定量，作为肾损伤与KIT评分的相关性。 在最后阶段，将进行数据分析，以比较 COVID-19阳性和COVID-19阴性人群，并识别肾损伤风险较高的人群， 重点关注COVID 19状态、既往肾脏疾病史/风险因素以及地理、人口统计学和种族 变化量

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.