[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Kidney](https://durgical.com/en/general-pathology/areas/kidney/) › Membranous nephropathy: PLA2R, subepithelial deposits and spikes # 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. Updated Nov 12, 2026 ## Key points - Commonest primary cause of nephrotic syndrome in many adult series; peak in middle age. - Anti-PLA2R antibodies in most primary cases; IgG4 is the dominant subclass. - LM: uniformly thick capillary walls without proliferation; silver shows spikes between deposits. - IF: granular IgG and C3 along the walls; EM: subepithelial deposits. - Secondary causes: lupus (class V), hepatitis B, carcinomas (lung, colon), drugs, other autoimmune disease. - High risk of renal vein thrombosis among nephrotic syndromes. ## 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. ## Memory aid Membranous is a coat, not a fire: thick walls, spikes, no cells, and a leak of protein. ## 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. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/membranous-nephropathy-pla2r-subepithelial-deposits-and-spikes/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Elsewhere in DurgiPedia - [Type III hypersensitivity (immune complexes)](https://durgical.com/en/immunology/type-iii-hypersensitivity/) - [Autoantibodies: the table to know](https://durgical.com/en/immunology/autoantibodies-the-table-to-know/) ## Connections ## Related 5 - [Immune mechanisms of glomerular injury](https://durgical.com/en/general-pathology/immune-mechanisms-of-glomerular-injury/) - [Glomerular diseases: comparison table](https://durgical.com/en/general-pathology/glomerular-diseases-comparison-table/) - [Lupus nephritis](https://durgical.com/en/general-pathology/lupus-nephritis/) - [Hepatitis B and D](https://durgical.com/en/general-pathology/hepatitis-b-and-d/) - [Paraneoplastic syndromes: the table to know](https://durgical.com/en/general-pathology/paraneoplastic-syndromes-the-table-to-know/) ## Related conditions 8 - [Membranous nephropathy](https://durgical.com/en/conditions/membranous-nephropathy/) - [Nephrotic syndrome](https://durgical.com/en/conditions/nephrotic-syndrome/) - [Systemic lupus erythematosus](https://durgical.com/en/conditions/systemic-lupus-erythematosus/) - [Viral hepatitis](https://durgical.com/en/conditions/viral-hepatitis/) - [Renal vein thrombosis](https://durgical.com/en/conditions/renal-vein-thrombosis/) - [Lupus nephritis](https://durgical.com/en/conditions/lupus-nephritis/) - [Lung cancer](https://durgical.com/en/conditions/lung-cancer/) - [Colorectal cancer](https://durgical.com/en/conditions/colorectal-cancer/) [← All of general pathology](https://durgical.com/en/general-pathology/) 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](https://medlineplus.gov/ency/article/000472.htm) (MedlinePlus, US National Library of Medicine, 2025). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/membranous-nephropathy-pla2r-subepithelial-deposits-and-spikes/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/membranous-nephropathy-pla2r-subepithelial-deposits-and-spikes/