The hypothesis that C3a is a key mediator for acute tubular injury in HUS is based on our data that C3a inhibition reduced apoptosis and restored megalin distribution in the proximal tubular cells, demonstrating that the activation of the C3a/C3aR signaling is not just an accompanying epiphenomenon but contributes directly to the pathogenesis of renal tubular injury in Stx2/LPS mice. Here, C3AR1 is linked to hemolytic-uremic syndrome.