The role of complement in kidney disease.

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 non-renal 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 significance and side effects of anti-complement therapy relevant to the general physician. © Royal College of Physicians 2020. All rights reserved.