Complement detection in kidney biopsies – utility and challenges

This review discusses the important role of staining for components of the complement cascade in both native and transplant kidney biopsies. The use of complement staining as a marker of prognosis, disease activity, and as a potential future tool in identifying patients who may benefit from complement-targeted therapies is discussed.While staining for C3, C1q and C4d can yield valuable information about complement activation in kidney biopsies, to adequately assess complement activation and potential therapeutic targets, expanded staining panels looking at multiple split products and complement regulatory proteins are needed. Recent progress has been made in identifying markers of disease severity in C3 glomerulonephritis and IgA nephropathy, such as Factor H-related Protein-5, which may serve as future tissue biomarkers. In the transplant setting, the limitation of relying on C4d staining to identify antibody mediated rejection is giving way to molecular diagnostics, including The Banff Human Organ Transplant (B-HOT) panel, which includes numerous complement complement-related transcripts, with the classical, lectin, alternative, and common pathways.Staining for complement components in kidney biopsies to understand how complement is activated in individual cases may help to identify patients who may benefit from complement-targeted therapies.