Chapter 8: Idiopathic membranoproliferative glomerulonephritis

BACKGROUND MPGN is a light-microscopic ‘‘pattern of injury’’ caused by many disorders (see Table 20). Patients commonly present with nephrotic syndrome, hypertension, glomerular hematuria, and progressive kidney dysfunction. Reduction in the serum concentration of complement components (C3 and/or C4) is commonly, but not uniformly, observed. MPGN can be further classified based on the extent and location of deposits of immunoglobulin and/or complement. The classification of MPGN according to ultrastructural appearances into MPGN type I, II, or III is commonly employed, but newer classification schema based on immunopathology are replacing this approach. Type I MPGN is associated with subendothelial and mesangial electron-dense deposits containing immunoglobulin and/or C3, and is often due to an underlying chronic hepatitis B or C infection (see Chapter 9); type II MPGN with electron dense intramembranous deposits containing numerous complement components, but not immunoglobulin and is now known as ‘‘dense-deposit disease’’. It has a distinctive etiology based on inherited or acquired abnormalities of complement regulatory proteins. Other rarer variants (type III MPGN) are also recognized based on abnormalities of the glomerular basement membrane and the location of electron-dense deposits. Immunopathological variants are recognized based on deposition of IgG and/or C3 component of complement in glomeruli. Those in which C3 is exclusively deposited are known as C3 GN. Treatment of MPGN is highly dependent on proper identification of underlying causes (see Table 20). In some patients C3 nephritic factor, an autoantibody to C3bBb, can be involved in the pathogenesis of type I, II, III, or C3 GN. Idiopathic MPGN is defined by exclusion of any other identifiable cause, most typically when the ultrastructural pattern is type I MPGN. Idiopathic type I MPGN is very uncommon in developed countries, but remains a relatively common, although diminishing, cause of nephrotic syndrome in developing countries, especially those with a high burden of endemic infectious diseases.