ArticlePflugers Archiv : European journal of physiology2025
ACE2 and TMPRSS2 in human kidney tissue and urine extracellular vesicles with age, sex, and COVID-19.
Article in Pflugers Archiv : European journal of physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Renal function dynamics in COVID-19: exploring biomarker interactions with D-dimer and C-reactive proteins.Bioscience reports · 2026Article
- Profiling of proteases involved in SARS-CoV-2 pathogenesis in human saliva: Influence of age and gender.Journal, genetic engineering & biotechnology · 2025Article
- Effects and regulation of ACE2 and TMPRSS2 abundance in healthy humans and in patients with SARS-CoV-2.Biochemical Society transactions · 2025Article
- Kidney Involvement in SARS-CoV-2 Infection: Peritoneal Dialysis as the Preferred Modality.Vaccines · 2025Review
- Diagnosis, Severity, and Prognosis from Potential Biomarkers of COVID-19 in Urine: A Review of Clinical and Omics Results.Metabolites · 2024Review
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Authors and funding
15 authors.
Funding
Abstract
SARS-CoV-2 virus infects cells by engaging with ACE2 requiring protease TMPRSS2. ACE2 is highly expressed in kidneys. Predictors for severe disease are high age and male sex. We hypothesized that ACE2 and TMPRSS2 proteins are more abundant (1) in males and with increasing age in kidney and (2) in urine and extracellular vesicles (EVs) from male patients with COVID-19 and (3) SARS-CoV-2 is present in urine and EVs during infection. Kidney cortex samples from patients subjected to cancer nephrectomy (male/female; < 50 years/˃75 years, n = 24; ˃80 years, n = 15) were analyzed for ACE2 and TMPRSS2 protein levels. Urine from patients hospitalized with SARS-CoV-2 infection was analyzed for ACE2 and TMPRSS2. uEVs were used for immunoblotting and SARS-CoV-2 mRNA and antigen detection. Tissue ACE2 and TMPRSS2 protein levels did not change with age. ACE2 was not more abundant in male kidneys in any age group. ACE2 protein was associated with proximal tubule apical membranes in cortex. TMPRSS2 was observed predominantly in the medulla. ACE2 was elevated significantly in uEVs and urine from patients with COVID-19 with no sex difference compared with urine from controls w/wo albuminuria. TMPRSS2 was elevated in uEVs from males compared to female. ACE2 and TMPRSS2 did not co-localize in uEVs/apical membranes. SARS-CoV-2 nucleoprotein and mRNA were not detected in urine. Higher kidney ACE2 protein abundance is unlikely to explain higher susceptibility to SARS-CoV-2 infection in males. Kidney tubular cells appear not highly susceptible to SARS-CoV-2 infection. Loss of ACE2 into urine in COVID could impact susceptibility and angiotensin metabolism.
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