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Key Clinical Updates in Membranous Nephropathy

The presence of elevated levels of circulating PLA2R antibodies, which are considered diagnostic for idiopathic membranous nephropathy, may eliminate the need for kidney biopsy.


  • Varying degrees of proteinuria.

  • Most common cause of primary adult nephrotic syndrome.

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

  • “Spike and dome” pattern on kidney biopsy from subepithelial deposits.

  • Secondary causes include hepatitis B virus and carcinomas.

Membranous nephropathy is the most common cause of primary nephrotic syndrome in adults, most often presenting in the fifth and sixth decades. It is an immune-mediated disease characterized by immune complex deposition in the subepithelial portion of glomerular capillary walls. The antigen in the primary form of the disease appears to be a phospholipase A2 receptor (PLA2R) on the podocyte in 70–80% of patients. Secondary disease is associated with infections, such as hepatitis B and C, endocarditis, and syphilis; underlying carcinomas (some of these cases may involve autoimmunity to podocyte-expressed thrombospondin type-1 domain-containing 7A [THSD7A]); autoimmune disease, such as SLE, mixed connective tissue disease, and thyroiditis; and certain drugs, such as NSAIDs and captopril. The course of disease is variable, with about 50% of patients progressing to ESRD over 3–10 years. Poorer outcome is associated with concomitant tubulointerstitial fibrosis, male sex, elevated serum creatinine, hypertension, and proteinuria greater than 10 g/day.

Patients with membranous nephropathy and nephrotic syndrome have a higher risk of hypercoagulable state than those with nephrosis from other etiologies; there is a particular predisposition to renal vein thrombosis in these patients.

A. Symptoms and Signs

Patients may be asymptomatic or may have edema or frothy urine. Venous thrombosis, such as an unprovoked deep venous thrombosis, may be an initial sign. There may be symptoms or signs of an underlying infection or neoplasm (especially lung, stomach, breast, and colon cancers) in secondary membranous nephropathy.

B. Laboratory Findings

Hypoalbuminemia and hyperlipidemia are characteristic laboratory findings in the nephrotic syndrome. Evaluation for secondary causes including serologic testing for SLE, syphilis, and viral hepatidites, and age- and risk-appropriate cancer screening should be performed. Elevated levels of circulating PLA2R antibodies is now considered diagnostic for idiopathic membranous nephropathy, and the presence of these may eliminate the need for kidney biopsy; additionally, titers can be followed during treatment. Kidney biopsy findings in membranous nephropathy include increased capillary wall thickness without inflammatory changes or cellular proliferation (eFigure 22–15); when stained with silver methenamine, a “spike and dome” pattern results from projections of excess GBM between the subepithelial deposits (eFigure 22–16). Immunofluorescence shows IgG and C3 staining along capillary loops (eFigure 22–17). Electron microscopy shows a discontinuous pattern of dense deposits along the subepithelial surface of the basement membrane.

eFigure 22–15.

Membranous glomerulonephritis. (H&E stain.) (Used, with permission, from Jean Olson, MD.)


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