Current approach to classification of membranoproliferative glomerulonephritis

Abstract

Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury, which historically has been classified using light and electron microscopic morphologic features. Primary (idiopathic) MPGN was divided into types I, II (dense deposit disease) and III, respectively defined by the presence of subendothelial deposits with capillary double contours, intramembranous electron dense material, or subepithelial and/or intramembranous deposits with or without basement membrane irregularities and subendothelial deposits. Secondary MPGN was associated with underlying diseases including infection, lymphoplasmacytic disorders, autoimmune disease, and malignancy. However, this classification encompasses entities with overlapping pathogenesis, clinical features, and treatment approaches. Therefore, classification of MPGN based on pathogenesis and associated immunofluorescence findings has been suggested. MPGN is divided into immune complex (IC)-mediated (immunoglobulin and complement deposition), complement (C)-mediated (C deposition) and non-IC, non-C-mediated forms. IC-mediated MPGN results from chronic antigenemia, including those previously designated type I, type III and secondary. C-mediated MPGN includes type II (dense deposit disease) and C3 glomerulonephritis, the latter with features of MPGN types I or III. Non-IC, non-C MPGN is secondary to few underlying causes, predominantly thrombotic microangiopathy of any cause. This classification allows for improved prognostic information and optimized approach to therapy. As pathogenesis is better understood, primary MPGN may cease to exist.