Nephropathy, Membranous

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

Diagnosis

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

Treatment

• 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

Outcome

Follow Up

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

Prognosis

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