Membranous nephropathy is a nephrotic syndrome characterised by thickening of the glomerular basement membrane due to subepithelial immune complex deposition.
It peaks between ages 50 and 60.
- Causes
- Idiopathic (primary disease)
- Infection
- Hepatitis B
- Malaria
- Syphilis
- Malignancy
- Lung cancer
- Lymphoma
- Leukaemia
- Drugs
- Gold
- Penicillamine
- NSAIDs
- Autoimmune disease
- Lupus nephritis (Class V disease)
- Thyroiditis
- Rheumatoid arthritis
- Pathophysiology
- Formation of antibodies against the M-type phospholipase A2 receptor 1 on podocytes → deposition of immune complexes in the glomerular basement membrane → complement activation and formation of the C5—C9 membrane attack complex → podocyte damage → loss of slit filter intergity → proteinuria
- Chronic inflammation → glomerulosclerosis → end-stage renal disease
- Signs and symptoms
- Peripheral oedema
- Frothy urine
- Microscopic haematuria
- Hypertension
- Other symptoms associated with secondary causes
- Differentials
- Investigations
- Urea and creatinine to estimiate eGFR
- Urinalysis
- Proteinuria > 3.5 g/day
- Microscopic haematuria
- Lipiduria
- Hyperlipidaemia
- Hypoalbuminaemia
- Renal ultrasound to assess the kidney size and structure and exclude other causes of kidney disease
- Serology
- ANA
- Anti-dsDNA
- Complement levels
- Hepatitis serology
- HIV testing
- Renal biopsy is the definitive diagnostic test
- Thickened glomerular basement without cellular proliferation in light microscopy
- Granular deposits of IgG and C3 along the capillary walls on immunofluorescence
- Subepithelial electron-dense deposits (’spike and dome’) on electron microscopy
- Treatment
- Proteinuria can spontaneously remit in patients with secondary disease
- ACE inhibitor or ARBs for proteinuria
- Immunosuppresion for those with a high-risk of progression
- Corticosteroids + cyclophosphamide/chlormabucil
- Anticoagulation for high-risk patients
- Complications
- Increased risk of infection due to loss of antibodies in urine
- Thromboembolic events, e.g., renal vein thrombosis
- Chronic kidney disease and end-stage renal disease
- Acute kidney injury
- Hypertension
- Dyslipidaemia and accelerated atherosclerosis
- Protein malnutrition