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For further information, see CMDT Part 22-19: Membranous Nephropathy

Key Features

Essentials of Diagnosis

  • Varying degrees of proteinuria

  • Most common cause of primary adult nephrotic syndrome

  • Significant risk for hypercoagulable state if nephrotic syndrome present

  • "Spike and dome" pattern on kidney biopsy from subepithelial deposits

  • Secondary causes include infections (eg, hepatitis B and C virus) and carcinomas

General Considerations

  • Most often presents in the fifth and sixth decades

  • An autoimmune disease with reactivity against several possible podocyte antigens

    • Circulating antibodies against the phospholipase A2 receptor (PLA2R) are present in 80% of cases

    • Reactivity against podocyte antigen thrombospondin type-1 domain-containing 7A (THSD7A) is present in about 10% of cases

  • Secondary disease is associated with

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

    • Underlying carcinomas (some of these cases may also involve autoimmunity to THSD7A)

    • Autoimmune disease, such as systemic lupus erythematosus (SLE), mixed connective tissue disease, and thyroiditis

    • Certain medications, such as nonsteroidal anti-inflammatory drugs and captopril

  • Patients with membranous nephropathy and nephrotic syndrome have a higher risk of hypercoagulable state with thrombosis than nephrosis from other etiologies. including a particular predisposition to renal vein thrombosis

Clinical Findings

  • May be asymptomatic

  • Edema

  • Frothy urine

  • Venous thrombosis may be an initial sign

  • Symptoms or signs of an underlying infection or neoplasm (especially lung, stomach, breast, and colon cancers) in secondary disease


Laboratory Findings

  • Hypoalbuminemia

  • Hyperlipidemia

  • Evaluation for secondary causes include

    • Serologic testing for SLE, syphilis, and viral hepatidites

    • Age- and risk-appropriate cancer screening

  • Elevated titer of circulating PLA2R antibodies is diagnostic

Diagnostic Procedures

  • Kidney biopsy findings

    • Increased capillary wall thickness without inflammatory changes or cellular proliferation

    • Silver methenamine stain: a "spike and dome" pattern resulting from projections of excess glomerular basement membrane (GBM) between the subepithelial immune complex deposits

    • Immunofluorescence shows IgG and C3 staining along capillary loops

    • Electron microscopy shows a discontinuous pattern of dense deposits along the subepithelial surface of the basement membrane


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

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

  • About 30% of patients with subnephrotic proteinuria (< 3 g/day) respond to antiproteinuric therapy with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker if blood pressure is > 125/75 mm Hg

  • Calcineurin inhibitors with or without corticosteroids may also be considered

  • Kidney transplantation


Follow Up

  • Reduction in proteinuria may take up to 6 months, especially with rituximab-based regimens


  • The course of primary disease is highly variable, with spontaneous remission in approximately 30% ...

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