Conditions · Nephrology and urology
Membranoproliferative glomerulonephritis !
A glomerular injury pattern in which immune deposits thicken the filter walls and cells multiply, often linked to hepatitis C or complement problems.
Updated 2026-11-01
Structures involved
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Why it happens
- Mediators of inflammation: the table to know
- Innate and adaptive immunity: overview
- Glomerulus and the filtration barrier: podocytes, mesangium, JGA
- Basement membrane
What it is
A pattern of glomerular injury seen on biopsy in which the capillary walls thicken and the mesangium proliferates, giving a lobular glomerulus and a "tram-track" (double-contour) basement membrane. It is now classified by whether immunoglobulins or only complement (C3) are deposited, which points to the cause.
Who gets it
Uncommon; seen in children and young adults when primary, and in adults when secondary to chronic infection. Chronic hepatitis C (often with cryoglobulinaemia) is the classic association; hepatitis B, endocarditis and chronic infections such as malaria or schistosomiasis matter in tropical regions, including parts of Latin America.
Causes
- Chronic infections: hepatitis C (with mixed cryoglobulinaemia), hepatitis B, infective endocarditis, infected shunts, malaria, schistosomiasis
- Autoimmune disease: systemic lupus erythematosus, Sjögren disease
- Monoclonal gammopathy and B-cell neoplasms such as chronic lymphocytic leukaemia
- Complement dysregulation (C3 glomerulopathy): C3 nephritic factor or inherited defects of alternative-pathway regulators
Risk factors
- Chronic hepatitis C or B infection
- Mixed cryoglobulinaemia
- Autoimmune disease or monoclonal gammopathy
- Family history of complement disorders; acquired partial lipodystrophy (dense deposit disease)
Pathophysiology
Immune complexes (or complement alone) deposit in the mesangium and subendothelial space and activate complement. Mesangial cells proliferate and extend between the endothelium and the basement membrane, laying down new membrane and producing the double contour. Inflammation and reduced filtering surface cause both nephritic and nephrotic features, and serum complement is often low.
Classification
- Immunoglobulin-mediated MPGN: immune complexes from chronic infection, autoimmunity or monoclonal gammopathy
- C3 glomerulopathy: dense deposit disease (formerly type II, intramembranous deposits, C3 nephritic factor) and C3 glomerulonephritis
- Older terms: type I (subendothelial deposits), type II (dense deposits), type III
Symptoms and signs
- Oedema and foamy urine from nephrotic-range proteinuria
- Haematuria, sometimes visible (cola-coloured urine)
- Hypertension
- Reduced urine output in nephritic presentations
- Features of the underlying cause: jaundice or liver disease, purpura and joint pain from cryoglobulins, fever from endocarditis
Diagnosis
- Clinical
- Nephritic or nephrotic presentation (often mixed) with hypertension; search for hepatitis, cryoglobulin, autoimmune and monoclonal causes.
- Tests
- Urinalysis with red cells, red-cell casts and proteinuria; creatinine; low C3 (and low C4 in immune-complex disease); hepatitis C and B serology, cryoglobulins, ANA and complement studies, serum and urine protein electrophoresis with free light chains. Kidney biopsy confirms the pattern: light microscopy (lobular, double contours), immunofluorescence (immunoglobulin versus C3 only) and electron microscopy (deposit location).
- Imaging
- Kidney ultrasound shows size and excludes other causes; normal or enlarged kidneys early.
Differential diagnosis
- Post-streptococcal glomerulonephritis (low C3 that normalises within weeks)
- Lupus nephritis
- IgA nephropathy
- Membranous nephropathy
- Thrombotic microangiopathy (can mimic double contours)
Goal of treatment
Treat the underlying cause, control proteinuria and blood pressure, and slow progression to chronic kidney disease.
Treatment
- Medical
- Treat the cause: direct-acting antivirals for hepatitis C, antivirals for hepatitis B, antibiotics for endocarditis, clone-directed therapy for monoclonal gammopathy.
- Medical
- Supportive kidney care: ACE inhibitors or ARBs to reduce proteinuria and blood pressure, diuretics for oedema, statins and salt restriction.
- Medical
- Immunosuppression (corticosteroids, mycophenolate, cyclophosphamide or rituximab) for idiopathic or severe progressive disease; complement inhibitors are being used for C3 glomerulopathy.
- Follow-up
- Monitoring of creatinine, proteinuria, complement levels and blood pressure.
- Procedure
- Dialysis or kidney transplant for kidney failure; C3 glomerulopathy often recurs in the graft.
Complications
- Progression to chronic kidney disease and kidney failure
- Nephrotic complications: thrombosis, infections, hyperlipidaemia
- Recurrence after kidney transplant
- Drusen-like retinal deposits in dense deposit disease
Prognosis
Variable. Secondary MPGN may improve when the cause (for example hepatitis C) is treated. Idiopathic disease and C3 glomerulopathy often progress, with many patients reaching kidney failure within about 10 years; heavy proteinuria, high creatinine and hypertension at diagnosis predict worse outcome.
Test yourself
Think of the answer, then tap the question to see it.
Which chronic infection is most classically linked to membranoproliferative glomerulonephritis?
Hepatitis C, often with mixed cryoglobulinaemia.
What is the characteristic light-microscopy finding of MPGN?
Lobular glomeruli with a split or double-contour basement membrane ("tram-track" appearance).
Which autoantibody is associated with dense deposit disease (C3 glomerulopathy)?
C3 nephritic factor, which stabilises the alternative-pathway C3 convertase and lowers serum C3.
How does MPGN differ from post-streptococcal GN in complement levels over time?
In post-streptococcal GN low C3 recovers within about 8 weeks; in MPGN it stays persistently low.
Related conditions
- Viral hepatitis
- Cryoglobulinemic vasculitis
- Nephrotic syndrome
- Post-streptococcal glomerulonephritis
- Rapidly progressive glomerulonephritis (anti-GBM, ANCA)
- Lupus nephritis
- Membranous nephropathy
- Infective endocarditis
- Chronic kidney disease
- Chronic lymphocytic leukaemia
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Glomerulonephritis: MedlinePlus Medical Encyclopedia (MedlinePlus (U.S. National Library of Medicine), 2024); C3 glomerulopathy: MedlinePlus Genetics (MedlinePlus (U.S. National Library of Medicine), 2024).
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