Membranoproliferative glomerulonephritis
Membranoproliferative glomerulonephritis is a rare chronic glomerulonephritis divided into immune-complex forms, most often driven by hepatitis C virus infection, and complement-mediated C3 glomerulopathies from alternative-pathway dysregulation, diagnosed by kidney biopsy with immunofluorescence. Treatment targets the underlying cause plus immunosuppression for nephrotic-range proteinuria or kidney dysfunction, and more than half of patients progress to end-stage kidney disease within 15 years.
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What this article covers
- Overview
A chronic glomerulonephritis defined by its injury pattern: membranoproliferative glomerulonephritis (MPGN) is a rare form of chronic glomerulonephritis, diagnosed primarily in children and young…
- Epidemiology
Rare overall, with a predilection for children and young adults: MPGN is diagnosed primarily in this age group, though secondary immune-complex forms occur across the adult age spectrum in association with chronic infections.
- Risk factors
Hepatitis C virus infection, particularly with concomitant cryoglobulinemia and small-vessel vasculitis, is the leading identifiable risk factor for immune-complex MPGN.
- Pathophysiology
The immune-complex form is driven by the classical complement pathway: circulating antigen-antibody complexes (for example from chronic HCV antigenemia) deposit in the glomerulus and activate C1q, C4, and C2, consuming both C3 and C4.
- Clinical features
Chronic glomerulonephritis is the typical presentation: most patients present insidiously with microscopic hematuria and subnephrotic proteinuria rather than an acute nephritic syndrome.
- Differential diagnosis
IgA nephropathy: recurrent gross hematuria 1-3 days after an upper respiratory infection, with normal serum complement levels, unlike the low C3/C4 typical of MPGN.
- Diagnosis
The diagnosis of MPGN is made by kidney biopsy, which shows the membranoproliferative injury pattern on light microscopy; the distinction between immune-complex and complement-mediated (C3…
- Management
First, treat the identifiable underlying cause when present, since this is disease-modifying: for HCV-associated MPGN, direct-acting antiviral therapy for hepatitis C is first-line; for…
- Complications
Progression to end-stage kidney disease: the most serious long-term complication, affecting more than half of patients within 15 years.
- Prognosis
Poor overall as a chronic glomerulonephritis: more than 50% of patients progress to ESKD within 15 years of diagnosis.
- Prevention
Screen and treat hepatitis C virus infection in at-risk populations (injection drug use, transactional sex, prior transfusion before 1992) to prevent HCV-associated immune-complex MPGN.
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