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For further information, see CMDT Part 22-18: Membranous Nephropathy

Key Features

  • Most common cause of primary nephrotic syndrome in adults

  • Caused by immune complex deposition in the subepithelial portion of glomerular capillary walls

  • Associated with

    • Underlying carcinomas

    • Infections, such as hepatitis B and C, endocarditis, syphilis

    • Autoimmune disease, such as systemic lupus erythematosus, mixed connective tissue disease, thyroiditis

    • Coagulopathy, eg, renal vein thrombosis, if nephrotic syndrome is present

    • Certain drugs, such as NSAIDs and captopril

  • Often presents in adults in the fifth and sixth decades

Clinical Findings

  • May be asymptomatic

  • Edema

  • Frothy urine

  • Venous thrombosis, such as an unprovoked deep venous thrombosis, may be an initial sign

  • Secondary disease associated with symptoms or signs of an underlying infection, such as hepatitis B and C, endocarditis, and syphilis


  • Evaluation for secondary causes including serologic testing for

    • Systemic lupus erythematosus

    • Syphilis

    • Viral hepatidites

    • Age- and risk-appropriate cancer screening

  • Elevated levels of circulating PLA2R antibodies

    • Considered diagnostic for idiopathic membranous nephropathy

    • The presence of these antibodies may eliminate the need for kidney biopsy

  • Kidney biopsy

    • Light microscopy: increased capillary wall thickness

    • Silver methenamine stain: a "spike and dome" pattern may be observed owing to projections of excess glomerular basement membrane between the subepithelial deposits

    • Immunofluorescence: IgG and C3 along capillary loops

    • Electron microscopy: discontinuous dense deposits along the subepithelial surface of the basement membrane


  • Underlying causes must be excluded prior to consideration of other treatment

  • Treatment of primary disease depends on the risk of progression of kidney disease

  • Conservative management includes therapy with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker if blood pressure is > 125/75 mm Hg to prevent or ameliorate proteinuria

  • Use of immunosuppressive agents should be limited to those with salvageable kidney function who are at highest risk for progression of kidney disease

  • Patients with nephrotic syndrome despite 6 months of conservative management and serum creatinine < 3.0 mg/dL (265 mcmol/L) may elect therapy with rituximab or with corticosteroids and cyclophosphamide for 6 months

  • Calcineurin inhibitors with or without corticosteroids may also be considered

  • Kidney transplantation

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