Conditions · Nephrology and urology
Focal segmental glomerulosclerosis !
Focal segmental glomerulosclerosis (FSGS) is scarring of some kidney filters. It causes protein loss in the urine and often progresses to kidney failure.
Updated 2026-11-01
Structures involved
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In the clinical exam
Why it happens
- Tissue repair: regeneration or scar; labile, stable and permanent cells
- Fibrosis in organs: TGF-β and the myofibroblast
- Glomerular filtration: the barrier and its determinants
- Glomerulus and the filtration barrier: podocytes, mesangium, JGA
What it is
A pattern of podocyte injury in which some glomeruli (focal) show scarring in part of the tuft (segmental). It usually presents as nephrotic syndrome or heavy proteinuria and is a leading glomerular cause of kidney failure.
Who gets it
It is one of the most common causes of nephrotic syndrome in adults and the most frequent in people of African ancestry, partly linked to APOL1 gene variants. Secondary forms related to obesity, HIV, sickle cell disease and reduced nephron mass are relevant in Latin America, and FSGS is an important cause of steroid-resistant nephrotic syndrome in children.
Causes
- Primary: circulating permeability factors injuring podocytes
- Genetic: podocyte protein genes (NPHS1, NPHS2) and APOL1 risk variants
- Virus-associated: HIV (collapsing variant), parvovirus B19, COVID-19
- Drug-associated: heroin, anabolic steroids, interferon, lithium, pamidronate
- Adaptive (hyperfiltration): obesity, reduced nephron mass, reflux nephropathy, sickle cell disease
Risk factors
- African ancestry (APOL1 variants)
- Obesity
- HIV infection
- Sickle cell disease
- Low birth weight or a single kidney
- Family history of kidney disease
Pathophysiology
Podocytes are injured by circulating factors, genetic defects, viruses, toxins or excess glomerular pressure. Because podocytes cannot regenerate, the bare basement membrane sticks to Bowman capsule and segments of the tuft collapse and scar. Proteinuria is non-selective, and progressive scarring reduces filtration until chronic kidney disease develops.
Classification
- By cause: primary, genetic, secondary (virus, drug, adaptive) and of undetermined cause
- Histological variants (Columbia): not otherwise specified, perihilar, cellular, tip, collapsing
- Collapsing variant (HIV, COVID-19) has the worst prognosis; tip variant the best
Symptoms and signs
- Swelling of the legs, face or abdomen
- Foamy urine
- Weight gain
- High blood pressure (more common than in minimal change disease)
- Sometimes microscopic haematuria
- Secondary forms may show subnephrotic proteinuria without marked oedema
Diagnosis
- Clinical
- Nephrotic or heavy proteinuria in an adult, or a child who does not respond to steroids; history for obesity, HIV, drugs, sickle cell disease and family history.
- Tests
- Urine protein-to-creatinine ratio, serum albumin, lipids, creatinine and eGFR; HIV, hepatitis B and C serology; kidney biopsy showing segmental sclerosis on light microscopy and foot-process effacement on electron microscopy (diffuse in primary, patchy in adaptive forms). Genetic testing in children, steroid-resistant or familial cases.
- Imaging
- Kidney ultrasound before biopsy; small echogenic kidneys suggest advanced chronic disease.
Differential diagnosis
- Minimal change disease (may be missed if the sample lacks scarred glomeruli)
- Membranous nephropathy
- Diabetic kidney disease
- Hypertensive nephrosclerosis
- Alport syndrome and other hereditary nephropathies
Goal of treatment
Reduce proteinuria, slow loss of kidney function, treat the underlying cause and control blood pressure and cardiovascular risk.
Treatment
- Medical
- Primary FSGS: glucocorticoids first, then calcineurin inhibitors if resistant or not tolerated; rituximab or other agents in selected cases.
- Medical
- All forms: ACE inhibitors or ARBs, and often SGLT2 inhibitors, to lower proteinuria and pressure; statins for dyslipidaemia; antiretroviral therapy in HIV-associated FSGS.
- Lifestyle
- Weight loss in obesity-related FSGS, low-salt diet and smoking cessation.
- Procedure
- Dialysis or kidney transplantation in kidney failure; primary FSGS can recur in the graft and may need plasmapheresis.
- Follow-up
- Monitoring: blood pressure, weight and oedema, urine protein and kidney function on a schedule, and adverse effects of immunosuppressants.
Complications
- Progression to end-stage kidney disease
- Recurrence after kidney transplantation
- Venous thromboembolism and infections
- Hypertension and cardiovascular disease
- Complications of immunosuppression
Prognosis
Variable. Complete remission of proteinuria predicts good long-term kidney survival, while persistent nephrotic-range proteinuria, the collapsing variant and steroid resistance carry a high risk of kidney failure within years.
Test yourself
Think of the answer, then tap the question to see it.
Which infection is classically associated with the collapsing variant of FSGS?
HIV infection (HIV-associated nephropathy).
What is the most common cause of nephrotic syndrome in adults of African ancestry?
Focal segmental glomerulosclerosis, partly related to APOL1 variants.
What does light microscopy show in FSGS?
Sclerosis of part of the tuft in some glomeruli (focal and segmental).
Which FSGS form classically recurs in the transplanted kidney?
Primary FSGS, attributed to a circulating permeability factor.
Related conditions
- Nephrotic syndrome
- Minimal change disease
- HIV infection and AIDS
- Obesity
- Sickle cell disease
- Chronic kidney disease
- Kidney transplant rejection
- Arterial hypertension
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Focal segmental glomerulosclerosis: MedlinePlus Medical Encyclopedia (MedlinePlus (U.S. National Library of Medicine), 2024); Nephrotic Syndrome in Adults (NIDDK (National Institutes of Health), 2024).
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