Definition
Membranous nephropathy (MN) is an immune-mediated glomerular disease characterised by subepithelial immune complex deposition along the glomerular basement membrane (GBM). It is the commonest cause of nephrotic syndrome in older Caucasian adults and a favourite MRCP topic because of its distinctive serology and histology.
Pathophysiology
In primary (idiopathic) MN, circulating autoantibodies — most often anti-phospholipase A2 receptor (anti-PLA2R) — bind a podocyte antigen, forming immune complexes in situ on the outer (subepithelial) aspect of the GBM. Complement activation damages podocytes, increasing glomerular permeability to protein.
Secondary MN results from immune complexes related to an underlying condition — malignancy, infection (hepatitis B), autoimmune disease (SLE, class V lupus nephritis), or drugs.
Clinical presentation
- Nephrotic syndrome: heavy proteinuria (>3.5 g/24h), hypoalbuminaemia, oedema, hyperlipidaemia.
- A significant minority present with sub-nephrotic proteinuria found incidentally.
- Venous thromboembolism is a notable complication — MN carries one of the highest thrombotic risks of any glomerular disease (loss of antithrombin III and other regulatory proteins). Renal vein thrombosis is classic.
Investigations
| Test | Typical finding |
|---|---|
| Urinalysis | Heavy proteinuria; bland sediment |
| Serum albumin | Low |
| Anti-PLA2R antibody | Positive in ~70–80% of primary MN |
| Renal biopsy | Subepithelial deposits; GBM ‘spikes’ on silver stain; granular IgG + C3 |
| Screen for secondary causes | Hepatitis B/C serology, ANA, age-appropriate cancer screening |
Management
Management balances supportive therapy with immunosuppression in higher-risk patients:
- Supportive: ACE inhibitor or ARB to reduce proteinuria and blood pressure, dietary sodium restriction, statin, and consideration of anticoagulation if serum albumin is very low.
- Immunosuppression: reserved for those at high risk of progression — persistent heavy proteinuria, rising creatinine, or high/rising anti-PLA2R titres. Rituximab has become a first-line option; calcineurin inhibitors and the historical cyclophosphamide-based (Ponticelli) regimens remain alternatives.
- Treat the secondary cause where identified — this alone may induce remission.
MRCP-specific traps
- Anti-PLA2R positive + nephrotic syndrome in an older adult points strongly to primary MN — but never forget to screen for malignancy in secondary disease.
- MN is the glomerular disease most associated with renal vein thrombosis — watch for sudden loin pain, haematuria, or a deteriorating renal function.
- Class V lupus nephritis is membranous in pattern; check ANA/anti-dsDNA if there are systemic features.
Summary
Membranous nephropathy is subepithelial immune complex disease causing nephrotic syndrome, typically in older adults. Anti-PLA2R supports primary disease; always exclude malignancy, hepatitis B and SLE. Treat supportively, anticoagulate the profoundly hypoalbuminaemic, and reserve immunosuppression (increasingly rituximab) for progressive disease.