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Kidney Week

Abstract: FR-PO165

Influenza A(H1N1)pdm09 Reaches the Kidney, Altering Immune Responses Without Causing Direct Tissue Injury

Session Information

  • AKI: Mechanisms - II
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Stowell-Connolly, Holly, University of Bristol Faculty of Health Sciences, Bristol, Bristol, United Kingdom
  • Lay, Abigail Charlotte, University of Bristol Faculty of Health Sciences, Bristol, Bristol, United Kingdom
  • Burt, Rachel, University of Bristol Faculty of Health Sciences, Bristol, Bristol, United Kingdom
  • Oliver, Elizabeth, University of Bristol School of Cellular and Molecular Medicine, Bristol, Bristol, United Kingdom
  • Goenka, Anu, University of Bristol School of Cellular and Molecular Medicine, Bristol, Bristol, United Kingdom
  • Coward, Richard, University of Bristol Faculty of Health Sciences, Bristol, Bristol, United Kingdom

Group or Team Name

  • Bristol Renal
Background

In 2009, a novel Influenza A(H1N1) virus caused the first pandemic of the twenty-first century. Patients commonly presented mild phenotypes, similar to seasonal influenza, however some developed complications requiring hospitalisation. Often critically ill patients exhibited major renal sequalae of acute kidney injury (AKI), leading to renal failure. Injury progression is poorly understood, with debates over development originating from direct viral infection of renal cells or pre-renal systemic inflammation.

Methods

Renal tissue and urine was taken from Babraham pigs (n=54) either daily (0-13 days) or weekly (0-3 weeks) following intranasal Influenza A(H1N1)pdm09 infection. IHC determined histological status of kidney tissue. Influenza A mRNA and nucleoprotein were detected by in situ hybridisation and IHC, respectively. Presence of H1N1 mRNA within urine was determined using qRT-PCR. Localised renal pro-/anti-inflammatory cytokine expression profiles were developed using qRT-PCR. CD4+ and CD8α+ T-cell infiltration and IgA deposition were detected by IF.

Results

Viral mRNA and protein was detected within kidney tissue at 1-6 days post-infection, similar to the timeline in respiratory tissue. Despite this, IHC revealed microscopic renal structure to be unchanged at all time points, with no evidence of necrosis/fibrosis. Consistent with this, pro-inflammatory cytokine mRNA decreased one-week post-infection (TNF-α, IFN-β, IFN-γ, and IL-4; p<0.05). Expression recovers after 7-14 days, often reaching levels greater than control (TNF-α, IFN-γ, IL-2, IL-4; p<0.05). Interstitial infiltration of CD4+ and CD8α+ cells, together with glomerular deposition of IgA, follows a similar trend (CD4 and IgA p<0.05). Urine samples were absent of H1N1 mRNA.

Conclusion

This work creates an infection timeline within the porcine renal system and highlights the ability of the influenza A(H1N1)pdm09 virus to reach the kidney without causing direct injury. Viral presence within renal tissue is cleared one-week post-infection, corresponding with a localised dampening of the immune system. This work demonstrates a direct role of Influenza A(H1N1)pdm09 in the kidney, and with current literature documenting AKI in COVID-19 patients, it is important to understand how respiratory viruses can contribute to AKI and mortality.

Funding

  • Government Support – Non-U.S.