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

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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.