Mechanisms of Disease: the complement system in renal injury - new ways of looking at an old foe

The fact that the complement system is activated during immune-complex glomerular disease has been known for nearly 50 years. Detection of complement deposition in the glomerulus using immunochemistry has become an important element of the histological analysis of renal biopsies, and is key to the diagnosis of many types of glomerulonephritis. In recent years it has become evident that complement activation is involved in the pathogenesis of other types of renal disease; complement activation is implicated in transplant injury, atypical hemolytic uremic syndrome and progressive tubulointerstitial fibrosis. Emergence of this evidence has provided insight into how these diseases develop, and has yielded useful diagnostic tools and potential targets for therapeutic intervention. Clinicians have, by using plasma-based therapies, unknowingly treated abnormalities of the complement system in renal patients for many years. Advances in antibody and protein technologies have led to the development of complement inhibitors that have been used in phase III clinical studies. More-specific agents and applications are likely to be developed over the coming years and are discussed in this Review.