Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Sepsis following kidney transplantation is a frequent complication due to mandatory immunosuppression and increased infection risk. Kidney transplant recipients who develop sepsis show inferior patient survival with reduced allograft function. Studies of sepsis-induced AKI suggest that responses to tubular injury with an uncontrolled pro-inflammatory response can further renal damage. DJ-1 is a known anti-oxidant protein that is expressed in the brain, kidney, and immune cells. The role of DJ-1 in sepsis is not clear. AKI is one of the common sepsis-associated pathologies, and there is no data on the role of DJ-1 in septic AKI.
*Methods: Wildtype and DJ-1 knockout mice both on B6 background were treated with 6.5mg/kg LPS (i.p.) with serum and tissue collected 24 hours later. Renal function and injury, as well as markers for inflammation were studied. Primary renal tubules (RTEC) were collected from both strains to study activation as well as cytotoxic serum responses.
*Results: Compared to WT mice, DJ-1(-/-) mice were more susceptible to LPS-induced AKI as indicated by higher plasma creatinine (WT LPS .61 ± 0.11 Vs DJ-1(-/-) LPS 0.87 ± 0.23; p= 0.0006) and Kidney Injury Marker-1 (KIM-1). Markers of renal inflammation (s100A8 and s100A9) and Reactive Oxidant/Nitrogen Stress (ROS/RNS) were increased in renal tissue of DJ-1 deficient mice. The increased oxidative stress was found to lead to increased Daxx-dependent apoptosis in the renal tubules.
*Conclusions: Our data suggests DJ-1 plays an important protective role in against sepsis-associated renal inflammation and injury through ROS/RNS control and preventing Daxx-dependent apoptosis and modulation of DJ-1 could help prevent transplant allograft injury during episodes of sepsis.
To cite this abstract in AMA style:Leeds J, Scindia Y, Ghias E, Cechova S, Loi V, Mandziak E, Swaminathan S. Lack of Dj-1 Amplifies Sepsis-Associated Acute Kidney Injury and Increases Parenchymal Apoptosis [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/lack-of-dj-1-amplifies-sepsis-associated-acute-kidney-injury-and-increases-parenchymal-apoptosis/. Accessed September 29, 2020.
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