Abstract: FR-PO122
Modulation of Oxidative Stress Prevents Deleterious Lung Kidney Interactions in a Novel Experimental Model of Pulmonary Renal Syndrome
Session Information
- AKI: Mechanisms - Inflammation/Sepsis/Remote Injury
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Author
- Farahmand, Firoozeh, Saint Louis, Saint Louis, Missouri, United States
Background
AKI is the most common organ dysfunction in acute lung injury (ALI) and ARDS. In fact, AKI increases the mortality rate to more than 40%, with the rate rising with AKI severity. Deleterious interactions between kidney and lung play a major role in multiorgan failure in critically ill patients. But, the casual relationships between lung injury and kidney injury is not well understood. Large body of evidence suggests oxidative stress mediates lung-kidney organ crosstalk. However, specific therapies are lacking. Since ALI/AKI, once initiated, is much less susceptible to treatment we need to investigate potential protective treatment which requires developing experimental model to translate drug findings from bench to bedside.
Methods
In a novel model of ALI/AKI induced by a toxic alkaloid( Tox-ALK) injection to evaluate the effects of antioxidant treatment, rats were treated with an Angiotensin II Type 1( AT1) receptor blocker with antioxidant activity daily starting a week before and continued for 1 wk post-(Tox-ALK) injection. Serial echocardiography was performed weekly to non-invasively monitor evolution of pulmonary hypertension secondary to lung injury. At 4 weeks lungs and kidneys were analyzed for antioxidant enzyme activities including superoxide dismutase, glutathione peroxidase, catalase and oxidative stress. Lungs wet/dry weight ratios were measured to assess edema. After sacrificing the animals, the renal cortex and the lung were removed for histology
Results
At 4 wks post-Tox-ALK, there was acute lung injury, characterized by lung edema, neutrophil infiltration, hypoxemia and acute tubular necrosis in the Kidney. Losartan treatment attenuated Tox-ALK induced oxidative stress in lung and the kidney, ALI, PH and importantly, increased the activities of SOD and GSHPx in the lung and the kidney.
Conclusion
In this experimental model ALI and AKI in rats correlates with a decrease in antioxidant and increase in oxidative stress in the lung & the kidney. Inhibition of the RAS prevent ALI and AKI , improved survival as well as oxidative stress parameter in the kidney. This study suggest the beneficial effects of AT1 receptor blocker as a kidney–lung protective strategy in critically ill patients.