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Updated: Jul 22, 2025

Single-channel Analysis and Calcium Imaging in the Podocytes of the Freshly Isolated Glomeruli
Published on: June 27, 2015
SuPAR mediates viral response proteinuria by rapidly changing podocyte function
Changli Wei1, Prasun K Datta2, Florian Siegerist3,4
1Department of Medicine, Rush University Medical Center, Chicago, IL, USA. changli_wei@rush.edu.
Abstract:
Elevation in soluble urokinase receptor (suPAR) and proteinuria are common signs in patients with moderate to severe coronavirus disease 2019 (COVID-19). Here we characterize a new type of proteinuria originating as part of a viral response. Inoculation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes increased suPAR levels and glomerulopathy in African green monkeys. Using an engineered mouse model with high suPAR expression, inhaled variants of SARS-CoV-2 spike S1 protein elicite proteinuria that could be blocked by either suPAR antibody or SARS-CoV-2 vaccination. In a cohort of 1991 COVID-19 patients, suPAR levels exhibit a stepwise association with proteinuria in non-Omicron, but not in Omicron infections, supporting our findings of biophysical and functional differences between variants of SARS-CoV-2 spike S1 protein and their binding to podocyte integrins. These insights are not limited to SARS-CoV-2 and define viral response proteinuria (VRP) as an innate immune mechanism and co-activation of podocyte integrins.
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