Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Oct 27;12(11):2600.
doi: 10.3390/diagnostics12112600.

Exploring Urinary Extracellular Vesicles and Immune Mediators as Biomarkers of Kidney Injury in COVID-19 Hospitalized Patients

Thalia Medeiros  1   2 , Lilian Santos Alves  1 , Mauro Jorge Cabral-Castro  1   3 , Alice Ramos Oliveira Silva  1 , Analúcia Rampazzo Xavier  1   2 , Dylan Burger  4 , Jorge Reis Almeida  1   5 , Andrea Alice Silva  1   2
Affiliations

Exploring Urinary Extracellular Vesicles and Immune Mediators as Biomarkers of Kidney Injury in COVID-19 Hospitalized Patients

Thalia Medeiros et al. Diagnostics (Basel). .

Abstract

Kidney injury is an important outcome associated with COVID-19 severity. In this regard, alterations in urinary extracellular vesicles (uEVs) could be detected in the early phases of renal injury and may be reflective of the inflammatory process. This is an observational study performed with a case series of COVID-19 hospitalized patients presenting mild-to-critical disease. Total and podocyte-derived uEVs were identified by nanoscale flow cytometry, and urinary immune mediators were assessed by a multiplex assay. We studied 36 patients, where 24 (66.7%) were considered as mild/moderate and 12 (33.3%) as severe/critical. Increased levels of total uEVs were observed (p = 0.0001). Importantly, total uEVs were significantly higher in severe/critical patients who underwent hemodialysis (p = 0.03) and were able to predict this clinical outcome (AUC 0.93, p = 0.02). Severe/critical patients also presented elevated urinary levels (p < 0.05) of IL-1β, IL-4, IL-6, IL-7, IL-16, IL-17A, LIF, CCL-2, CCL-3, CCL-11, CXCL-10, FGFb, M-CSF, and CTAcK. Lastly, we observed that total uEVs were associated with urinary immune mediators. In conclusion, our results show that early alterations in urinary EVs could identify patients at higher risk of developing renal dysfunction in COVID-19. This could also be relevant in different scenarios of systemic and/or infectious disease.

Keywords: COVID-19; cytokines; extracellular vesicles; hemodialysis; urine.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Urinary total and podocyte-derived EVs in COVID-19 hospitalized patients and healthy controls. (A) Flow cytometry gating strategy shows EV identification based on calibration with size beads (100 nm–900 nm) and representative dot plots demonstrate the characterization of total uEVs (Annexin V+) and podocyte-derived uEVs (Annexin V+ Podoplanin+) in a healthy control (HC) and in a patient with COVID-19. (B) Comparison of uEVs between HC and COVID-19 patients. (C) Comparison of total uEVs according to COVID-19 severity and need for hemodialysis. Differences between groups were assessed using Mann–Whitney test.
Figure 2
Figure 2
ROC curves of total uEVs, proteinuria, and albuminuria for the prediction of hemodialysis as a clinical outcome in COVID-19 severe/critical patients. ACR = albumin-to-creatinine ratio; AUC = area under the curve; Cr = creatinine; Ptn = protein; u = urinary.
Figure 3
Figure 3
Landscape of urinary immune mediators in healthy controls and COVID-19 hospitalized patients. The z-score for each mediator was calculated by subtracting the observed value by the mean and dividing by the standard deviation.
See this image and copyright information in PMC

References

    1. Chan L., Chaudhary K., Saha A., Chauhan K., Vaid A., Zhao S., Paranjpe I., Somani S., Richter F., Miotto R., et al. AKI in Hospitalized Patients with COVID-19. J. Am. Soc. Nephrol. 2021;32:151–160. doi: 10.1681/ASN.2020050615. - DOI - PMC - PubMed
    1. Durvasula R., Wellington T., McNamara E., Watnick S. COVID-19 and Kidney Failure in the Acute Care Setting: Our Experience From Seattle. Am. J. Kidney Dis. 2020;76:4–6. doi: 10.1053/j.ajkd.2020.04.001. - DOI - PMC - PubMed
    1. Cheng Y., Luo R., Wang K., Zhang M., Wang Z., Dong L., Li J., Yao Y., Ge S., Xu G. Kidney Disease Is Associated with In-Hospital Death of Patients with COVID-19. Kidney Int. 2020;97:829–838. doi: 10.1016/j.kint.2020.03.005. - DOI - PMC - PubMed
    1. Lim J.-H., Park S.-H., Jeon Y., Cho J.-H., Jung H.-Y., Choi J.-Y., Kim C.-D., Lee Y.-H., Seo H., Lee J., et al. Fatal Outcomes of COVID-19 in Patients with Severe Acute Kidney Injury. J. Clin. Med. 2020;9:1718. doi: 10.3390/jcm9061718. - DOI - PMC - PubMed
    1. Pramod S., Kheetan M., Ogu I., Alsanani A., Khitan Z. Viral Nephropathies, Adding SARS-CoV-2 to the List. Int. J. Nephrol. Renov. Dis. 2021;14:157–164. doi: 10.2147/IJNRD.S303080. - DOI - PMC - PubMed