C3 glomerulopathy (C3G) is a rare autoimmune glomerulopathy that has historically been classified as type II membranoproliferative glomerulonephritis (MPGN). It may show a range of clinical findings and so should be considered in the differential diagnosis of any patient presenting with glomerulonephritis.
Synonym: glomerulopathy with dominant C3 deposits
Mechanism: abnormal activation, deposition or degradation of complement
Pathology:
(1) deposition of C3 fragments in the glomeruli with dominant immunostaining for C3c (staining intensity 2 orders of magnitude greater than any other immune reactant)
(2) osmophilic electron-dense deposits on electron microscopy
Subgroups:
(1) dense deposit disease (DDD): linear electron-dense deposits in the middle layer of the glomerular basement membrane
(2) C3 glomerulonephritis (C3GN)
(3) CFHR5 nephropathy
Clinical features:
(1) often preceded by an infectious episode
(2) usually presents with persistent hematuria (micro or macro) with or without proteinuria (which may be light or heavy)
(3) frequent progression to end-stage kidney disease if untreated
(4) recurrence after renal transplantation
Laboratory findings:
(1) low serum C3 and C4
(2) low serum complement factor H
(3) presence of a monoclonal protein
(4) presence of C3 nephritic factor (C3NeF)
(5) abnormal complement factor H-related protein 5 (CFHR5)
