Membranous nephropathy

Definition

Membranous nephropathy (membranous glomerulonephritis) is characterized by deposition of immune complexes on the outer side of the glomerular basement membrane (subepithelial) with thickening of the basement membrane. It mainly affects adults, in whom it is a common cause of nephrotic syndrome.

Aetiopathogenesis

In the primary form, the M-type phospholipase A2 receptor (PLA2R) on podocytes is the main antigen of the deposited immune complexes.

Secondary forms occur with:

• cancer (in 6–15% of patients), e.g. carcinomas of the lung, prostate, colon, stomach, breast and kidney, lymphomas, chronic lymphocytic leukemia, melanoma
• infections: hepatitis B and C, syphilis, HIV, malaria, schistosomiasis
• autoimmune diseases: systemic lupus erythematosus, thyroiditis
• certain drugs, e.g. NSAIDs

In children the disease is rare and usually secondary, e.g. to chronic hepatitis B, lupus or autoimmune thyroid disease.

Clinical features

Typical is a nephrotic syndrome of insidious onset with edema; nephrotic-range proteinuria is present in about 80%. The urine sediment is usually bland, occasionally with microscopic hematuria and hypertension; kidney function is often normal initially.

Renal vein thrombosis is more frequent in membranous nephropathy than in other glomerulopathies. It is often silent but may cause flank pain, hematuria and hypertension and may lead to pulmonary embolism.

Histology

Electron microscopy shows subepithelial electron-dense deposits, between which the basement membrane grows outward as "spikes" (silver stain). Later, the deposits lie within the markedly thickened basement membrane. Immunofluorescence shows diffuse granular IgG deposition along the capillary walls without cellular proliferation or necrosis. In the primary PLA2R-positive form IgG4 predominates, in cancer-associated forms IgG1 and IgG2.

Diagnosis

• basic workup of nephrotic syndrome: protein-to-creatinine ratio, serum albumin, lipids, creatinine and eGFR
• serum anti-PLA2R antibodies to distinguish primary from secondary forms
• kidney biopsy to confirm the diagnosis
• search for secondary causes: age-appropriate cancer screening (especially with weight loss, anemia or older age), hepatitis B and C serology, antinuclear antibodies, drug history

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Further reading (open access)

1. MSD Manual Professional: Membranous Nephropathy

Cross-references