Membranous nephropathy: PLA2R, subepithelial deposits and spikes
- Lesion
Antibodies bind an antigen on the podocyte surface and deposit beneath it, thickening the capillary wall and causing nephrotic syndrome in adults.
What it is
Membranous nephropathy is a leading cause of nephrotic syndrome in adults. In most primary cases, autoantibodies bind the phospholipase A2 receptor (PLA2R) on podocytes; a few target other podocyte antigens such as THSD7A. Secondary forms follow lupus, hepatitis B, solid tumours, some drugs and other autoimmune diseases. Complement C5b-9 injures the podocyte without inflammation, so the disease is a leak, not a nephritis.
Structure
- Early: capillary walls look normal or slightly stiff; the deposits are seen only by IF and EM.
- Middle: basement membrane grows between deposits (spikes), then over them, giving a thick, moth-eaten wall.
- Late: deposits are reabsorbed, the wall stays thick, and segmental and global sclerosis appear.
- No proliferation or neutrophils: a clue that this is not a nephritis.
Step by step
- Autoantibodies (often IgG4) bind PLA2R or another antigen on the podocyte foot process.
- Complexes form in place and shed into the subepithelial space.
- Complement is activated; C5b-9 inserts into podocyte membranes.
- Injured podocytes lay down new basement membrane around the deposits (spikes) and their foot processes efface.
- The barrier leaks protein: nephrotic syndrome; slow scarring follows in some patients.
Clinical notes
- Insidious edema and frothy urine in an adult; hematuria and hypertension are mild or absent.
- About a third of primary cases remit spontaneously; another part progresses slowly.
- In an older patient, search for an occult cancer; in Latin America, check for hepatitis B and lupus.
In the lab
- Serum anti-PLA2R antibodies support primary disease and track activity; PLA2R staining can be done on the biopsy.
Test yourself
Think of the answer, then tap the question to see it.
What antigen is targeted in most primary membranous nephropathy?
The phospholipase A2 receptor (PLA2R) on podocytes.
What produces the spikes seen on silver stain?
New basement membrane laid down by podocytes between the subepithelial deposits.
What are three secondary causes of membranous nephropathy?
Systemic lupus (class V), hepatitis B infection and solid carcinomas; certain drugs are another.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Membranous nephropathy: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.