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

Abstract: The incidence of AKI is 20-30% in patients hospitalized with COVID-19 in the United States, andis over 40% in patients admitted to the ICU. Moreover, the mortality rate in patients thatexperience AKI in the setting of COVID-19 is approximately 2- to 10-fold higher than patientswithout AKI. The pathogenesis of AKI in COVID-19 infection remains unclear and it is not knownif the injury to the tubule is direct result of the virus infection or if it is secondary to other organcomplications. Availability of urine, blood and tissue samples early in the course of infection willprovide important pathogenic insights for therapeutic and clinical management.The Translational Research investigating Biomarker Endpoints (TRIBE)-AKI consortium has along-standing history of conducting multidisciplinary epidemiologic and translational researchstudies in the setting of AKI. They have experience with long term follow-up of hospitalizedpatients, tissue and sample handling as well as analytic considerations. We propose aprospective observational study of the clinical and biologic predictors of major adverse kidneyevents 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 kidneydisease.We will examine consecutive patients hospitalized with COVID-19 at three premier academichospitals participating in the TRIBE consortium: Johns Hopkins Medicine, Mount Sinai Hospitaland Yale-New Haven Hospital. We assess the incidence, severity, and clinical predictors ofMAKE-D during hospitalization and at 90 days following discharge. We will investigate thepossible role of injury, inflammation and repair mechanisms through biomarkers in the bloodand urine in serial samples collected from patients during hospitalization. We will also performadvanced evaluation of kidney biopsies using single cell RNA sequencing to identify possiblemechanistic disease pathways, which may lead to novel therapeutic targets.Combating this pandemic will require a multidisciplinary approach from the medical researchcommunity, including rigorously conducted epidemiologic studies that include granular patient-level data and translational research studies to understand the pathogenesis of COVID-associated kidney disease.