membranoproliferative

Membranoproliferative glomerulonephritis (MPGN) is a pattern of glomerular injury seen in several diseases. It is characterized by mesangial cell proliferation and thickening of the glomerular capillary walls, often producing a double-contour or tram-track appearance on light microscopy. Immunofluorescence and electron microscopy reveal immune deposits and characteristic subendothelial, mesangial, or intramembranous deposits. Clinically, MPGN may present with hematuria, proteinuria (sometimes at nephrotic levels), hypertension, and varying kidney function.

Pathogenesis and classification have historically relied on electron microscopy and immunofluorescence patterns. MPGN types I–III describe distinct deposit locations: Type I usually shows subendothelial and mesangial immune deposits; Type II (dense deposit disease) features dense intramembranous deposits with C3-dominant staining; Type III shows both subepithelial and subendothelial deposits. In current practice, MPGN is often categorized as immune complex–mediated MPGN or C3 glomerulopathy, the latter arising from dysregulation of the alternative complement pathway (for example, C3 nephritic factor or factor H abnormalities). Triggers for immune complex MPGN include chronic infections such as hepatitis C, cryoglobulinemia, and autoimmune diseases.

Diagnosis is by kidney biopsy. Light microscopy typically shows mesangial expansion and endocapillary proliferation, with double-contour walls. Immunofluorescence reveals granular IgG, IgM, and C3 in immune complex MPGN, while C3 glomerulopathy shows C3 with little or no immunoglobulin. Electron microscopy localizes deposits to subendothelial, subepithelial, or intramembranous compartments.

Treatment targets the underlying cause and kidney protection. Immune-modulating therapy may be used for immune complex MPGN; antiviral treatment is important for hepatitis C–associated disease. Complement inhibitors are being explored for C3 glomerulopathy. Prognosis varies, with risk of progression to chronic kidney disease in affected individuals.