MPGN is manifested histologically by alterations in the GBM and mesangium and by proliferation of glomerular cells. It accounts for 5% to 10% of cases of idiopathic nephrotic syndrome in children and adults. Some patients present only with hematuria or proteinuria in the nonnephrotic range; others exhibit a combined nephroticnephritic picture. In the past, MPGN was subclassified into two types (I and II) on the basis of distinct ultrastructural, immunofluorescence, light microscopic, and pathogenic findings. These are now recognized to be distinct entities, termed MPGN type I and dense deposit disease (formerly MPGN type II). Of the two types of disease, MPGN type I is far more common (about 80% of cases) and is discussed here. Dense deposit disease will be discussed later along with the related condition of C3 glomerulonephritis.
Type I MPGN may be caused by deposition of circulating immune complexes or by in situ immune complex formation with a planted antigen. The inciting antigen is not known.
MORPHOLOGYBylightmicroscopytheglomeruliarelarge,haveanaccentuatedlobularappearance,andshowproliferation of mesangial and endothelial cells as well as infiltrating leukocytes (
Fig.
14.8A ).TheGBMisthickened,andtheglomerularcapillarywalloftenshowsadoublecontour,or“tramtrack,”appearance,especiallyevidentwithuseofsilverorperiodicacid–Schiff(PAS)stains.This“splitting”oftheGBMisduetoextensionofprocessesofmesangialandinflammatorycellsintotheperipheralcapillaryloopsanddepositionofmesangialmatrixaswellassubepithelialimmunecomplexes(see
Fig.14.8B ).Thecharacteristiclightmicroscopicglomerularmanifestationsareoftenreferredtoasmembranoproliferative pattern of glomerular injury.
Byelectronmicroscopy,typeIMPGNischaracterizedbydiscrete subendothelial deposits (see
Fig.14.8B ).Byimmunofluorescencemicroscopy,C3isdepositedinanirregulargranularpattern,andIgGandearlycomplementcomponents(C1qandC4)alsooftenarepresent,indicativeofanimmunecomplexpathogenesis.
The mode of presentation in approximately 50% of cases is the nephrotic syndrome, although it may begin as acute nephritis or mild proteinuria. The prognosis generally is poor. In one study, none of the 60 patients followed for 1 to 20 years showed complete remission; 40% progressed to end-stage renal failure, 30% had variable degrees of renal insufficiency, and the remaining 30% had persistent nephrotic syndrome without renal failure. MPGN type I also may occur in association with other disorders (secondary MPGN), such as systemic lupus erythematosus, hepatitis B and C, chronic liver disease, and chronic bacterial infections. Indeed, many so-called “idiopathic” cases are believed to be associated with hepatitis C and related cryoglobulinemia.
Fig. 14.8 (A)Membranoproliferativeglomerulonephritis(MPGN),showingmesangialcellproliferation,basementmembraneduplication,leukocyteinfiltration,andaccentuationoflobulararchitecture.(B)SchematicrepresentationofthetwopatternsofMPGN.IntypeI,therearesubendothelialdeposits;intypeII,nowcalleddense deposit disease, intramembranouscharacteristicallydensedepositsareseen.Inbothtypes,mesangialinterpositiongivestheappearanceofsplitbasementmembraneswhenviewedbylightmicroscopy.
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