Complement in Kidney Disease: Core Curriculum 2026.

The complement cascade is part of the innate immune system, and it provides an important line of defense against infections. Inappropriate or excessive activation of this system, however, is also a driver of kidney inflammation in many diseases. Complement inhibitory drugs have now been approved by the US Food and Drug Administration for the treatment of 5 renal diseases: atypical hemolytic uremic syndrome, C3 glomerulopathy, immune-complex membranoproliferative glomerulonephritis, antineutrophil cytoplasmic antibody-associated vasculitis, and IgA nephropathy. Ongoing clinical trials are testing new anticomplement drugs and additional renal indications for complement inhibitors. Most immunosuppressive drugs do not directly block complement activation, and the use of complement inhibitors for renal indications is likely to expand in the coming years. Complement activation in renal diseases also generates plasma, urine, and tissue biomarkers, and laboratory evaluation of the complement system is an important part of the clinical work-up of patients with these inflammatory and autoimmune conditions. It is essential, therefore, that nephrologists are familiar with the available anticomplement drugs and with complement diagnostics.