The complement cascade in renal pathology

Abstract

The complement cascade comprises avariety of soluble and cell surface proteins and is an important component of the innate immune system. When the cascade is triggered by any of the three activation pathways, the complement system rapidly produces large amounts of protein fragments that are potent mediators of inflammatory, vasoactive, and metabolic responses. All activation pathways lead to the terminal complement cascade with the formation of the membrane attack complex, which lyses cells by forming membrane pores. Although the complement system is essential for pathogen defense and homeostasis, excessive or uncontrolled activation can lead to tissue damage. Recent research shows that the complement system is activated in almost all kidney diseases, even those not traditionally considered immune-mediated. In directly complement-mediated kidney diseases, complement factors or regulators are defective, afunctional or inactivated by antibodies. In many other renal diseases, the complement system is activated secondarily as aresult of renal damage and is therefore involved in the pathogenesis of the disease, but is not the trigger. The detection of complement deposits is also used to diagnose kidney disease. This review describes the structure of the complement system and the effects of its dysregulation as acause and modulator of renal disease.