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

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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.