Complement activation is a crucial driver of acute kidney injury in rhabdomyolysis

Rhabdomyolysis is a life-threatening condition caused by skeletal muscle damage with acute kidney injury being the main complication dramatically worsening prognosis. Specific treatment for rhabdomyolysis-induced lacking and mechanisms of are unclear. To clarify this, we studied intra-kidney complement activation (C3d C5b-9 deposits) in tubules vessels patients mice injury. The lectin pathway was found to be activated kidney, likely via an abnormal pattern Fut2-dependent cell fucosylation, recognized recognition molecule collectin-11 this proceeded C4-independent, bypass manner. Concomitantly, myoglobin-derived heme alternative pathway. Complement deposition were attenuated pre-treatment scavenger hemopexin. This indicates that unique double-trigger mechanism, pathways. direct pathological role demonstrated preservation function C3 knockout after induction rhabdomyolysis. transcriptomic signature included strong inflammatory apoptotic component, which C3/complement-dependent, as they normalized mice. macrophage population expressed complement-sensitive phenotype, overexpressing CD11b C5aR1. Thus, our results demonstrate Hence, scavenging inhibition represent promising therapeutic strategies.