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Abstract: SA-PO074

Lung-Kidney Injury Caused by Innate Derived Mediator suPAR

Session Information

  • AKI: Mechanisms - III
    November 05, 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

  • Suresh Kumar, Varsha, Rush University Medical Center, Chicago, Illinois, United States
  • Altintas, Mehmet M., Rush University Medical Center, Chicago, Illinois, United States
  • Wei, David Changli, Rush University Medical Center, Chicago, Illinois, United States
  • Mokhlesi, Babak, Rush University Medical Center, Chicago, Illinois, United States
  • Liptay, Michael J., Rush University Medical Center, Chicago, Illinois, United States
  • Reiser, Jochen, Rush University Medical Center, Chicago, Illinois, United States

Group or Team Name

  • Division of Nephrology and Rush Lung Center, Rush University Medical Center
Background

Soluble urokinase plasminogen activator receptor suPAR is an innate-immune system derived circulating kidney disease risk factor that has its highest physiological expression at baseline in the upper airway. Critical illnesses with high mortality rates often exhibit both acute lung and kidney injury as complications. The objective of our study is to understand whether murine pulmonary airway injury can induce kidney injury, perhaps in a suPAR dependent manner.

In the injured human lung, uPAR is documented in several pathological respiratory conditions including COPD, pneumonia and tuberculosis and recently also in COVID-19. Since suPAR levels increase prior to and during kidney injury, we aimed to explore a lung-kidney connection.

Methods

Injection of naphthalene, an aromatic hydrocarbon present in tobacco smoke constitutes a well-characterized model for acute airway injury in mice. SuPAR over-expressing mice (suPARTg) and UPAR knockout mice (UPARKO) were injected intraperitoneally with naphthalene. To begin to explore mechanisms of lung-kidney axis, lung lavage and serum inflammation was assessed by multi-plex ELISA and flow cytometry.

Results

SuPAR overexpression accelerated mortality in naphthalene injured mice by 40%. Furthermore, injecting an UPAR antibody in naphthalene injured suPARTg mice increased led to significant reduction in mortality. UPARKO mice exhibited a 100% survival rate post injury. Increased survival observed in UPARKO mice could be attributed to significantly increased IL6 levels in both lung lavage and serum, thereby altering the outcome of naphthalene mediated injury.

Conclusion

In conclusion, immune derived factors such as suPAR connect the lung with the kidney. Targeting suPAR may be beneficial in increasing survival in cases where mortality may be attributed to multi-organ failure induced by lung injury.

Funding

  • NIDDK Support