Rhabdomyolysis and complement—once again, epithelial cells take center stage

Rhabdomyolysis is frequently associated with kidney injury. Unfortunately, there are no specific treatments for this condition, and patient care primarily consists of supportive measures. In this edition of Kidney International, Boudhabhay et al. demonstrate that myoglobin released from injured skeletal muscle cells triggers tubulointerstitial complement activation. In a mouse model of the disease, interventions that scavenged free heme or that prevented complement activation ameliorated kidney injury, raising the possibility that these strategies may be effective treatments for the condition. Rhabdomyolysis is frequently associated with kidney injury. Unfortunately, there are no specific treatments for this condition, and patient care primarily consists of supportive measures. In this edition of Kidney International, Boudhabhay et al. demonstrate that myoglobin released from injured skeletal muscle cells triggers tubulointerstitial complement activation. In a mouse model of the disease, interventions that scavenged free heme or that prevented complement activation ameliorated kidney injury, raising the possibility that these strategies may be effective treatments for the condition. Complement activation is a crucial driver of acute kidney injury in rhabdomyolysisKidney InternationalVol. 99Issue 3PreviewRhabdomyolysis is a life-threatening condition caused by skeletal muscle damage with acute kidney injury being the main complication dramatically worsening the prognosis. Specific treatment for rhabdomyolysis-induced acute kidney injury is lacking and the mechanisms of the injury are unclear. To clarify this, we studied intra-kidney complement activation (C3d and C5b-9 deposits) in tubules and vessels of patients and mice with rhabdomyolysis-induced acute kidney injury. The lectin complement pathway was found to be activated in the kidney, likely via an abnormal pattern of Fut2-dependent cell fucosylation, recognized by the pattern recognition molecule collectin-11 and this proceeded in a C4-independent, bypass manner. Full-Text PDF