Complement and the Kidney: An Overview

The complement cascade was first recognized as a downstream effector system of antibody-mediated cytotoxicity. Consistent with this view, it was discovered in the 1960s that complement is activated in the glomeruli of patients with immune complex glomerulonephritis. More recently, research has shown that complement system has many additional functions relating to regulation of the immune response, homeostasis, and metabolism. It has also become clear that the complement system is important to the pathogenesis of many non-immune complex mediated kidney diseases. In fact, in atypical hemolytic uremic syndrome and C3 glomerulopathy, uncontrolled complement activation is the primary driver of disease. Complement activation generates multiple pro-inflammatory fragments, and if not properly controlled it can cause fulminant tissue injury. Furthermore, the mechanisms of complement activation and complement-mediated injury vary from disease to disease. Many new drugs that target the complement cascade are in clinical development, so it is important to fully understand the biology of the complement system and its role in disease.