The term C3 glomerulopathy encompasses two conditions, dense deposit disease (formerly MPGN, type II) and C3 glomerulonephritis. These are relatively rare diseases with certain shared clinical, morphologic, and pathogenic features that may be part of a spectrum of injury. They are set apart by differences in the electron microscopic appearance. Patients may present with nephrotic or nephritic syndrome, however, cases with only mild proteinuria also occur. Patients with dense deposit disease are usually younger and more likely to have low serum C3 levels than patients with C3 GN, although these distinctions are subtle.
Complement dysregulation due to acquired or hereditary abnormalities of the alternative pathway of complement activation is the underlying cause of dense deposit disease and C3 GN. Some patients have an autoantibody against C3 convertase, called C3 nephritic factor (C3NeF), that causes uncontrolled cleavage of C3 by the alternative complement pathway. In other patients, mutations in various complement regulatory proteins, such as Factor H, Factor I, and membrane cofactor protein (MCP), or auto-antibodies to Factor H, are the cause of unregulated activation of the alternative pathway of complement.
MORPHOLOGYAlthoughglomerularchangesindensedepositdiseaseandC3GNvaryfromrelativelysubtletosevere,theclassiclightmicroscopicpresentationissimilartothatseeninMPGN,type1.Theglomeruliarehypercellular,thecapillarywallsshowduplicatedbasementmembranes,andthemesangialmatrixisincreased.Byimmunofluorescencemicroscopy,thereisbright mesangial and glomerular capillary wall staining for C3 inbothdensedepositdiseaseandC3GN.Indensedepositdisease,C3stainingalsomaybeseenalongthetubularbasementmembranes.IgGandtheearlycomponentsoftheclassicalcomplementpathway(C1qandC4)areusuallyabsentinbothconditions.Byelectronmicroscopy,C3GNfeaturesmesangialandsubendothelialelectron-dense“waxy”deposits;similardepositsalsomaybeseenalongthetubularbasementmembranes.Bycontrast,intheaptlynameddensedepositdisease,thelaminadensaandthesubendothelialspaceoftheGBMaretransformedintoanirregular,ribbonlike,extremelyelectron-densestructure,resultingfromthedepositionofC3-containingmaterial.
Both dense deposit disease and C3 GN carry a relatively poor prognosis and both tend to recur posttransplantation at a rate of up to 85%. In a recent study of 70 patients with dense deposit disease or C3 GN, 29% of patients progressed to end-stage renal failure after a median of 28 months.
Acute postinfectious GN is caused by glomerular deposition of immune complexes resulting in proliferation of and damage to glomerular cells and infiltration of leukocytes, especially neutrophils. The classic pattern is seen in poststreptococcal GN. Infections by organisms other than streptococci also may be associated with postinfectious GN. These include certain pneumococcal and staphylococcal infections as well as several common viral diseases such as mumps, measles, chickenpox, and hepatitis B and C.
The typical case of poststreptococcal GN develops in a child 1 to 4 weeks after he or she recovers from a group A streptococcal infection. Only certain “nephritogenic” strains of β-hemolytic streptococci evoke glomerular disease. In most cases, the initial infection is localized to the pharynx or skin. In rare cases, the disease can develop during the infection.