The role of complement in kidney disease

Abstract

While the complement cascade is an important component of the innate immune system, uncontrolled activation can cause severe disease. This concept is illustrated by the prototypical complement-mediated renal disease atypical haemolytic uraemic syndrome (aHUS), which causes renal failure if untreated but when managed with the complement inhibitor eculizumab leaves the patient vulnerable to infection with encapsulated organisms. Complement activation is also implicated in the pathogenesis of many other renal and nonrenal diseases, necessitating an understanding of complement biology and diagnostics. We review renal diseases in which complement over-activation is known to cause tissue injury; aHUS and C3 glomerulopathy. We also discuss the contribution of complement more widely to the pathophysiology of renal disease, and highlight the signifi cance and side effects of anti-complement therapy relevant to the general physician.