Membranous Nephropathy (Membranous Glomerulonephritis)
Content of This Page
1- Definition & Types
2- Causes (Aetiology)
3- Pathophysiology
4- Clinical Features & Examination
5- Investigations
6- Management
7- Complications
8- Core Concepts
Definition & Types
Membranous nephropathy (MN) is a chronic immune-mediated glomerular disease characterized by:
Thickened glomerular basement membranes (GBM) without significant hypercellularity.
Subepithelial immune complex deposits.
It typically presents with nephrotic syndrome.
Types:
Primary (Idiopathic) – ~70–80%
Autoantibodies to podocyte antigens, especially PLA2R1.
Secondary – ~20–30%
Associated with infections, malignancies, drugs, or autoimmune diseases.
Causes (Aetiology)
Primary (Idiopathic):
Autoantibodies to phospholipase A2 receptor 1 (PLA2R1) on podocytes.
Less commonly, THSD7A antibodies.
- Secondary causes:
Category Examples Infections Hepatitis B & C, syphilis, HIV Autoimmune Systemic lupus erythematosus Malignancy Solid tumours (lung, colon, breast), lymphomas Drugs NSAIDs, penicillamine, gold Toxins Heavy metals (e.g. mercury)
Pathophysiology
Antibodies (esp. anti-PLA2R) target podocyte antigens.
Immune complexes form in situ or are planted subepithelially.
Complement activation (C5b-9 membrane attack complex) damages podocytes.
Leads to proteinuria due to loss of selective permeability.
GBM thickening occurs without inflammatory cell infiltration.
-Key Morphology:
Light microscopy: Thick GBM
Immunofluorescence: Granular IgG & C3 along GBM
EM: Subepithelial electron-dense deposits
Clinical Features & Examination
Classic Presentation:
Nephrotic syndrome:
Generalised oedema (especially periorbital)
Frothy urine (due to proteinuria)
Weight gain from fluid retention
No hematuria or hypertension initially (often “bland” urine)
Signs on Examination:
Oedema (ankle, sacral)
Signs of hypoalbuminaemia (e.g. ascites, pleural effusion)
Look for clues of secondary causes:
Lymphadenopathy (malignancy)
Hepatosplenomegaly (infection)
Rash or arthritis (autoimmune)
Investigations
A. Urine tests:
Proteinuria >3.5 g/day or PCR >350 mg/mmol
Microscopy: Typically bland, occasional hyaline casts
B. Blood tests:
↓ Albumin, ↑ cholesterol, ↑ triglycerides
Urea & creatinine for renal function
Anti-PLA2R antibodies (positive in 70–80% of idiopathic cases)
C. Imaging:
Renal ultrasound: May show normal or increased kidney size in nephrotic state
D. Renal biopsy:
Definitive diagnosis
Confirms immune complex deposition and GBM thickening
Management
Supportive (initial for all):
Salt and fluid restriction
ACE inhibitors/ARBs to reduce proteinuria
Statins for hyperlipidaemia
Anticoagulation (if serum albumin <25 g/L due to thrombotic risk)
Diuretics for oedema
🧪 Specific (immunosuppressive) – for high-risk or progressive disease:
Corticosteroids + cyclophosphamide
Rituximab (anti-CD20 monoclonal antibody) – increasingly used
Monitor anti-PLA2R levels to track response
Complications
Thromboembolism (e.g. renal vein thrombosis, DVT/PE)
Infections (especially with immunosuppression or urinary loss of Ig)
Progressive CKD or ESRD (up to 1/3 of patients)
Relapse after remission
Treatment side effects: infections, cytopenias, malignancy risk (e.g. cyclophosphamide)
Core Concepts
| Key Point | Detail |
|---|---|
| Most common nephrotic cause in adults | Especially in Caucasian males |
| PLA2R antibodies | Highly specific for primary MN |
| Bland urine | Unlike other GN – no haematuria/casts |
| Risk stratification critical | Not all need immunosuppression |
| Biopsy needed | Confirms diagnosis and excludes other GNs |
| 30–35% may remit spontaneously | Close monitoring essential |