#5524 THE ROLE OF C5AR VERSUS C3 IN THROMBOTIC MICROANGIOPATHY, ISCHEMIC KIDNEY NECROSIS, AND ACUTE KIDNEY INJURY INDUCED BY CHOLESTEROL CRYSTAL EMBOLISM

Abstract Background and Aims Certain thrombotic microangiopathies (TMA) respond to inhibition of complement factor C5, which abrogates formation the membrane attack complex hence impairs host defense. Inhibition C5a receptor (C5aR) avoids this safety problem still controls autoimmune systemic vasculitis. We speculated that targeting C5aR could be sufficient also in TMA, e.g., related cholesterol crystal embolism (CCE). Method induced experimental TMA C3-/-, C5aR-/- or wildtype mice by injecting CC into left kidney artery analyzed angiopathy, drop measured glomerular filtration rate (GFR), ischemic necrosis 24 hours after CCE. Results In mice, injection caused diffuse followed a consistent GFR compared baseline necrosis. Genetic deficiency C3 convertase profoundly attenuated indicating key role system CCE-related TMA. same extent provides main contribution pathogenesis Conclusion conclude C5a/C5aR axis attenuate for better profile would expected as C5 inhibition.