Membranous glomerulonephritis

Membranous glomerulonephritis is the commonest type of glomerulonephritis in adults and is the third most common cause of end-stage renal failure (ESRF). It usually presents with nephrotic syndrome or proteinuria.

Causes

• idiopathic: due to anti-phospholipase A2 antibodies
• infections: hepatitis B, malaria, syphilis
• malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia
• drugs: gold, penicillamine, NSAIDs
• autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid

Diagnosis

• anti-PLA2R antibodies → positive in ~70–80% of idiopathic membranous nephropathy
• screen for secondary causes:
  • hepatitis B, C, HIV
  • SLE (ANA, anti-dsDNA)
  • malignancy (esp. solid tumours: lung, colon, breast)
  • drugs (NSAIDs, gold, penicillamine)
• renal biopsy is needed for a definite diagnosis:
  • electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits. This creates a 'spike and dome' appearance

Silver-stained section showing thickened basement membrane, subepithelial spikes

Management

• all patients should receive an ACE inhibitor or an angiotensin II receptor blocker (ARB):
  • these have been shown to reduce proteinuria and improve prognosis
• immunosuppression
  • as many patients spontaneously improve only patient with severe or progressive disease require immunosuppression
  • corticosteroids alone have not been shown to be effective. A combination of corticosteroid + another agent such as cyclophosphamide is often used
• consider anticoagulation for high-risk patients

Prognosis - rule of thirds

• one-third: spontaneous remission