Podocyte-Specific Protein Expression in Urine Exosome Acts as a Marker for Renal Injury in Post-COVID State

Document Type

Journal Article

Publication Date

3-18-2025

Journal

Metabolic syndrome and related disorders

DOI

10.1089/met.2024.0199

Keywords

long-COVID; podocytopathy; urine exosomes

Abstract

Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) has been associated with the development of COVID-19. COVID-19 may cause endothelial cell dysfunction (ECD), which can lead to cardiometabolic diseases and podocytopathy. In this study, we explored whether presence of hyperglycemia predisposes to SARS-CoV-2 infection, in vitro, and whether COVID-19 can put an individual at a higher risk of persistent renal damage in the long-term following acute COVID infection. To estimate renal damage, we evaluated albuminuria and podocytopathy. Podocytopathy was estimated by measuring podocyte-specific protein levels in urine-derived exosomes from patients who were admitted with acute COVID-19 at 10 days, 6 months, and 12 months post-acute SARS-CoV-2 infection. Blood and urine samples from patients with SARS-CoV-2 post-infection were procured from the George Washington University COVID repository. Peripheral blood mononuclear cells and urine exosomes were isolated. Podocyte-specific proteins Podocalyxin (PODXL) and Nephrin (NEPH) were identified from urine exosomes. Urine exosomal podocalyxin levels were significantly high at 10 week (n = 18; P = 0.001), 6 month (n = 25; P = 0.003) and 12 month (n = 14; P = 0.0001) time points. Nephrin levels were also noted to be high at 10 week (n = 18; P = 0.001) and 12 month (n = 14; P = 0.007) time points, compared with urine samples obtained from type 2 diabetes subjects who never had COVID-19. Though urinary podocyte-specific proteins were high, compared to control, there were no significant differences noted on urine albumin:creatinine ratios (UACR) between the groups. Persistent high levels of podocyte-specific proteins noted in urinary exosomes even at 12 months post-Covid may lead to the development of chronic kidney disease.

Department

Medicine

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