This review provides an accurate and succinct account of the complement pathways and the regulators of the alternative pathway of complement activation. Would reference the consensus report for C3G (Pickering et al. Kidney Int. 2013)(Cook & Pickering, Nature Reviews Nephrology 2015). Care should be taken to utilize similar nomenclature and classifications delineated in the consensus report. MPGN is a histopathological lesion. C3G is a clinical diagnosis requiring evidence of complement dysregulation. The consensus report defines C3G (C3 glomerulopathy) as glomerular disorders with predominant glomerular C3 deposition on biopsy. The importance of this diagnosis is it’s association with genetic mutations and/or autoantibodies. C3G can be subdivided into dense deposit disease and C3GN based on electron microscopic findings. C3GN can be further subdivided by the histology seen by light microscopy. MPGN with dominant C3 is the predominant form of C3GN, but mesangioproliferation, endocapillary proliferation, and minimal change disease have all been reported.

The consensus report subdivides MPGN into 3 classes, based on immunofluorescence findings: i) Ig-mediated MPGN, ii) MPGN with dominant C3, and iii) idiopathic MPGN (not C3G and not Ig-associated). The diagnostic evaluation should differ based on the class. “In everyday practice, the morphological diagnosis of ‘glomerulonephritis with dominant C3’ is useful for identifying patients who require investigation of the complement pathway.” Patients with Ig-mediated MPGN should undergo evaluation for viral hepatitis, cryoglobulinemia, and monoclonal gammopathies. There are two publications that have validated the utility of this reclassification system in pediatric patients and they might be worth referencing (Okuda et al. Nephrology 2015 and Kawasaki et al. Pediatric Nephrol 2016).