Membranoproliferative glomerulonephritis (MPGN) is a rare form of chronic glomerulonephritis diagnosed primarily in children and young adults. The name stems from its pattern of glomerular injury. The entity is divided into immune-complex forms of MPGN (mediated by antigen-antibody interactions triggering the classical complement pathway) versus complement-mediated forms of MPGN (also termed C3 glomerulopathies, due to a hyperactive alternative complement pathway). An immune-complex MPGN, with or without cryoglobulinemia, is the classic form of kidney involvement seen in patients with hepatitis C virus infection. The alternative complement pathway abnormalities that drive the C3 glomerulopathies are either mutations in regulators (for example, complement factor H) or activators (for example, complement factor B) of the alternative pathway, or antibodies directed at regulator or activator complement proteins.
Although MPGN can rarely present as an acute and severe form of glomerulonephritis, the more common presentation is a chronic glomerulonephritis that initially manifests with microscopic hematuria and subnephrotic proteinuria. As disease progresses, proteinuria can reach nephrotic range, and kidney dysfunction ensues.
The diagnosis of MPGN is made by kidney biopsy. The distinction between immune-complex and complement-mediated MPGN is based on immunofluorescence microscopy, in which the absence of immunoglobulin staining signals an antibody-independent manner of triggering complement and hence alternative pathway hyperactivity.
Currently, treatment of MPGN is nonspecific and includes immunosuppression (for example, glucocorticoids) when nephrotic-range proteinuria and/or kidney dysfunction is present. The advent of complement-targeting therapies such as the C5 monoclonal antibody, eculizumab, may bring disease-specific therapy for the complement-mediated forms of MPGN.
The overall prognosis of MPGN as a chronic form of glomerulonephritis is poor, with >50% of patients progressing to ESKD within 15 years of diagnosis.