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Membranous Nephropathy

Membranous Nephropathy is a glomerular disease characterized by thickening of the glomerular basement membrane due to immune complex deposition. It is a common cause of nephrotic syndrome in adults.

Also called

Membranous glomerulopathy

ICD-10

N04.2

Specialty

Nephrology

Onset

Chronic

Reviewed

August 2026
On This Page

Overview

-Membranous Nephropathy is caused by immune-mediated injury to the glomerular filtration barrier, particularly the podocytes and Glomerular Basement Membrane (GBM).

-It may be:

  • Primary membranous nephropathy — most commonly associated with antibodies against phospholipase A2 receptor (PLA2R)
  • Secondary membranous nephropathy — associated with autoimmune disease, infections, malignancy, or certain medications

-The main clinical manifestation is proteinuria, often causing nephrotic syndrome.

Etiology & Risk Factors

-Etiology

–The disease results from immune complex formation along the glomerular basement membrane, causing podocyte injury and protein leakage.

 

-Major causes include:

  • Primary autoimmune disease, commonly involving anti-PLA2R antibodies
  • Systemic Lupus Erythematosus
  • Chronic infections
  • Malignancy
  • Certain medications

 

-Risk Factors:

  • Older age
  • Autoimmune disease
  • Chronic hepatitis B or other relevant infections
  • Malignancy
  • Exposure to causative medications

Pathophysiology

Autoantibody formation or secondary immune trigger → subepithelial immune complex deposition → complement activation → podocyte injury → glomerular basement membrane thickening → increased protein permeability → proteinuria → nephrotic syndrome → progressive kidney damage

Clinical Presentation

-Symptoms:

  • Frothy urine
  • Peripheral edema
  • Weight gain
  • Fatigue
  • Reduced urine output in severe disease

 

-Signs:

  • Peripheral or generalized edema
  • Hypertension
  • Features of nephrotic syndrome
Membranous Nephropathy Overview
Membranous Nephropathy Overview

History Taking

-Ask about:

  • Frothy urine and edema
  • Duration and progression of symptoms
  • Previous kidney disease
  • Symptoms of systemic lupus erythematosus or other autoimmune disease
  • Symptoms suggesting chronic infection
  • Unexplained weight loss or symptoms suggesting malignancy
  • Medication history
  • Previous thrombosis
  • Family history of autoimmune or kidney disease

Physical Examination

-General Examination

  • Blood pressure
  • Peripheral or generalized edema
  • Weight changes

 

-System-Specific Examination:

  • Signs of venous thrombosis
  • Features of autoimmune disease
  • Signs suggesting underlying malignancy or infection

Investigations

-Biochemistry / Specific Tests

  • Urinalysis

  • Urine protein-to-creatinine ratio or 24-hour urine protein

  • Serum albumin

  • Serum creatinine and eGFR

  • Lipid profile

  • Anti-PLA2R antibody testing

  • Tests for secondary causes when clinically indicated

 

-Imaging

Renal ultrasound may assess kidney structure and exclude other abnormalities.

 

–Additional imaging may be required when evaluating suspected malignancy or thrombosis.

 

-Special / Confirmatory Tests

Kidney biopsy is often used to confirm the diagnosis and assess histological features.

Typical findings include:

  • Diffuse thickening of the glomerular basement membrane

  • Subepithelial immune deposits

  • Granular immunoglobulin and complement deposition on immunofluorescence

Diagnosis

-Diagnosis is based on:

  • Significant proteinuria, often nephrotic-range
  • Hypoalbuminemia
  • Assessment of kidney function
  • Anti-PLA2R antibody testing
  • Evaluation for secondary causes
  • Kidney biopsy when required

 

A strongly positive anti-PLA2R antibody in an appropriate clinical setting may support the diagnosis of primary membranous nephropathy

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Management

1. Definitive Treatment

Treatment depends on the risk of progressive kidney disease.

  • Low-risk disease: supportive management and monitoring

  • Moderate- or high-risk disease: immunosuppressive therapy may be required

  • Secondary membranous nephropathy: treat the underlying cause

 

2 Medical Treatment

  • ACE inhibitors or ARBs to reduce proteinuria and control blood pressure

  • Diuretics for edema

  • Statins when indicated

  • Anticoagulation in selected high-risk patients

  • Rituximab for appropriate patients requiring immunosuppressive treatment

  • Cyclophosphamide-based therapy or calcineurin inhibitors in selected patients

 

3. Surgical / Procedural Treatment

No routine surgical treatment.

Kidney replacement therapy may be required if kidney failure develops.

 

4. Supportive Management

  • Sodium restriction

  • Blood pressure control

  • Reduction of proteinuria

  • Monitoring kidney function

  • Monitoring serum albumin and proteinuria

Complications

  • Nephrotic syndrome
  • Severe edema
  • Hypoalbuminemia
  • Hyperlipidemia
  • Venous thromboembolism
  • Renal vein thrombosis
  • Acute kidney injury
  • Progressive Chronic Kidney Disease (CKD)
  • Kidney failure

 

Prognosis

-The prognosis varies considerably. Some patients undergo spontaneous remission, while others develop persistent proteinuria and progressive kidney dysfunction

–Persistent heavy proteinuria, declining eGFR, and high disease activity are associated with a poorer prognosis.

Key Points / Clinical Pearls

  • Membranous Nephropathy is a common cause of nephrotic syndrome in adults.
  • It is characterized by immune-mediated podocyte injury.
  • Primary disease is commonly associated with anti-PLA2R antibodies.
  • Secondary causes include autoimmune disease, infection, malignancy, and medications.
  • Heavy proteinuria is the main clinical feature.
  • Edema and hypoalbuminemia are common in nephrotic syndrome.
  • Anti-PLA2R testing is important for diagnosis and monitoring.
  • Kidney biopsy may confirm the diagnosis and assess the disease.
  • Patients have an increased risk of venous thromboembolism.
  • ACE inhibitors or ARBs help reduce proteinuria.
  • Not all patients require immediate immunosuppressive therapy.
  • Rituximab is an important treatment option for appropriate patients.
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  • Fervenza FC, Appel GB, Barbour SJ, et al. Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. N Engl J Med. 2019;381(1):36-46. New England Journal of Medicine .
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Membranous Nephropathy . National Institutes of Health.
  • National Library of Medicine (NIH). Membranous Nephropathy . StatPearls.