Focal segmental glomerulosclerosis
- Lesion
Podocyte loss leaves scars in parts of some glomeruli. It is a pattern with many causes and a common route to kidney failure.
What it is
FSGS means sclerosis in part of the tuft in only some glomeruli. It arises whenever podocytes are lost faster than they can be replaced: a primary podocytopathy related to minimal change disease, adaptive stress after loss of nephrons or in obesity, gene variants in slit diaphragm proteins or APOL1, viruses such as HIV and SARS-CoV-2, heroin and sickle cell disease. It is a leading cause of nephrotic syndrome in adults, especially in people of African or Hispanic descent.
Structure
- Segments of the tuft collapse, with increased matrix, hyalinosis and foam cells; adhesion to Bowman capsule is common.
- IF: nonspecific trapping of IgM and C3 in the sclerotic segments.
- EM: foot process effacement, widespread in primary disease and patchy in adaptive disease; podocytes detach from the GBM.
- Collapsing variant: the whole tuft shrinks and podocytes swell and proliferate; tubules dilate into microcysts with protein casts.
Step by step
- Podocytes are injured by a circulating factor, a gene defect, a virus or mechanical strain.
- They efface, detach and are lost in the urine; adult podocytes barely divide.
- Bare GBM sticks to Bowman capsule and plasma proteins seep into the wall (hyalinosis).
- Matrix accumulates and capillary loops collapse: a segmental scar.
- Remaining glomeruli enlarge and their pressure rises, injuring more podocytes.
- The cycle spreads the scars to more glomeruli and ends in global sclerosis.
Clinical notes
- Proteinuria from nephrotic range to mild, plus hypertension and gradual loss of GFR.
- Primary FSGS can recur in a transplanted kidney, sometimes within hours.
- Adaptive FSGS has less edema and lower albumin than primary FSGS even with heavy proteinuria.
Test yourself
Think of the answer, then tap the question to see it.
Why can a biopsy miss FSGS?
Early lesions involve only some glomeruli, mainly deep juxtamedullary ones, so a small sample may contain none.
Which FSGS variant is linked with HIV infection?
Collapsing glomerulopathy, with tuft collapse, podocyte hyperplasia and microcystic tubules.
What do APOL1 risk variants explain?
The higher risk of FSGS and chronic kidney disease in people of African descent; the variants protect against some trypanosomes.
Elsewhere in DurgiPedia
Connections
Microorganisms1
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: Focal segmental glomerulosclerosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.