C3 Glomerulopathy (C3G) defines a group of complement-mediated renal diseases that share specific features identifiable on kidney biopsy the hallmark of which is C3 dominance on immunofluorescence by at least two orders of magnitude greater than any other immuno-reactant; electron microscopy is also specific. These features should prompt a thorough evaluation of the complement system that covers four domains: 1) genetic drivers of disease; 2) acquired drivers of disease; 3) biomarker profiling; and, 4) tests of complement function. The aggregate picture afforded by these studies provides insight into disease status and can guide treatment. Although optimal disease-directed treatment has not be determined, most patients should receive angiotensin‐converting enzyme inhibitors or angiotensin II receptor blocker for their anti-proteinuric and nephro-protective effects. The value of anti-cellular immune suppression to target T and/or B cells is controversial. The role of complement abnormalities has focused attention on anti-complement therapies as potential treatments and it is well documented that some, but not all, patients respond to eculizumab with elevation of soluble C5b-9 being a potentially useful marker of a responder to this terminal pathway blocker. No specific data are available to inform decisions surrounding transplantation. The development of novel complement inhibitors is a high priority for these patients.
KeywordsC3 glomerulopathy Dense deposit disease C3 glomerulonephritis Complement dysregulation alternative pathway
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