Nephropathy, Membranous

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

Diagnosis

• 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

Treatment

• 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