KLK4 and hereditary angioedema: Bradykinin is the main mediator of increased vascular permeability in patients with HAE [6] [7] During acute attacks of HAE, kallikrein is insufficiently inhibited because of the deficiency in C1-INH, the kallikrein-kinin system becomes activated, and at the end of the cascade, an increased amount of bradykinin is produced that results in the edema seen in patients with HAE.