Makindo Medical Notes | Focal Segmental Glomerulosclerosis (FSGS)

🧪 Focal Segmental Glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and chronic kidney disease worldwide. "Focal" → only some glomeruli are affected. "Segmental" → only part of each affected glomerulus shows sclerosis.

📘 About

One of the most common causes of end-stage renal disease (ESRD) globally.
Presents with proteinuria — nephrotic (>3.5 g/day) or sub-nephrotic.
Incidence is rising, with a significant public health burden.

🧬 Aetiology & Pathophysiology

Podocyte injury and depletion are the central mechanism → impaired filtration barrier → proteinuria.
Likely immune-mediated: possible circulating plasma factor (explains recurrence post-transplant & steroid responsiveness).
Genetic forms seen especially in children and young adults (e.g., podocin or nephrin mutations).
Shares features with Minimal Change Disease (MCD) but biopsy reveals segmental sclerosis.

🔍 Microscopy (Biopsy)

Segmental sclerosis in glomeruli, characteristic of FSGS

🎯 Renal biopsy: segmental sclerosis, hyalinosis, and podocyte effacement (on EM). Immunofluorescence may show IgM and C3 deposits.

📎 Associations

🏥 Nephropathies: reflux nephropathy, analgesic nephropathy.
🦠 Infections: HIV, malaria.
💉 Substances: IV heroin use.
🧬 Haemoglobinopathies: sickle cell disease.
⚖️ Other: severe obesity, adaptive response to reduced nephron mass.
🔄 Post-transplant recurrence: occurs in up to 30% of patients, often leading to graft loss.

👩‍⚕️ Clinical Presentation

Nephrotic syndrome: oedema, frothy urine, hypoalbuminaemia, hyperlipidaemia.
Hypertension is common (especially adults).
Microscopic haematuria in some cases.
Prothrombotic tendency → ↑ risk of DVT, PE, or renal vein thrombosis.

🔬 Investigations

Dipstick: proteinuria ± blood.
24h urine protein: quantifies nephrotic-range proteinuria.
U&Es: rising creatinine → renal impairment.
USS: kidneys usually normal size/echogenicity.
Biopsy (gold standard): focal & segmental sclerosis of glomerular tufts, mesangial expansion.

💊 Management

Immunosuppression:
- 1st-line: high-dose steroids (response variable).
- Ciclosporin or tacrolimus for steroid-resistant cases (monitor nephrotoxicity).
- Other agents: cyclophosphamide, mycophenolate (selected cases).
Supportive:
- ACE inhibitors / ARBs → reduce proteinuria and control BP.
- Lifestyle: weight reduction in obesity-related FSGS.
- Statins for dyslipidaemia.
- Anticoagulation if thrombosis risk high.
Advanced disease: dialysis or renal transplantation (but beware recurrence).

📉 Prognosis

Variable course: some remit, many progress to CKD/ESRD within 5–10 years.
Poor prognostic factors: high baseline proteinuria, resistance to steroids, renal impairment at diagnosis.

📖 References

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Focal Segmental Glomerulosclerosis (FSGS)