Focal segmental glomerulosclerosis (FSGS)
Focal segmental glomerulosclerosis is a podocytopathy causing segmental glomerular scarring on biopsy, presenting with nephrotic-range proteinuria and accounting for up to 40% of primary nephrotic syndrome in adults. Diagnosis requires kidney biopsy, and primary disease is treated with high-dose glucocorticoids followed by calcineurin inhibitors for resistant cases.
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What this article covers
- Overview
A podocytopathy causing segmental glomerular scarring: focal segmental glomerulosclerosis (FSGS) is a pattern of kidney injury defined by podocyte detachment and death leading to segmental sclerosis…
- Epidemiology
Most common nephrotic-syndrome biopsy finding in Black adults: individuals of African ancestry carry approximately a five times higher risk for FSGS than those of European descent, largely mediated by the apolipoprotein L1 (APOL1) gene.
- Risk factors
High-risk APOL1 genotype (African ancestry): the single strongest genetic risk factor, conferring roughly a 10-fold increased risk for FSGS, a 7-fold increased risk for hypertension-attributed ESKD…
- Pathophysiology
Podocyte injury is the initiating event: detachment and death of podocytes from the glomerular basement membrane leads to the segmental sclerosis that defines FSGS on light microscopy.
- Clinical features
Proteinuria in every patient, of variable severity: the defining clinical feature, ranging from severe nephrotic-range proteinuria with the full nephrotic syndrome to more modest, otherwise asymptomatic proteinuria.
- Differential diagnosis
Minimal change disease: the other major podocytopathy; distinguished on biopsy by normal light microscopy with only diffuse podocyte foot-process effacement on electron microscopy, and it is far more…
- Diagnosis
Diagnosis requires kidney biopsy: there is no serologic or clinical criteria set that establishes FSGS; the diagnosis is confirmed by light microscopy showing glomerulosclerosis (scarring) in a focal…
- Management
First, start conservative therapy in every patient regardless of subtype: Lisinopril, start 2.5-5 mg PO daily titrated to the maximal tolerated dose (or losartan 50-100 mg PO daily), to control proteinuria and blood pressure.
- Complications
End-stage kidney disease: the leading long-term complication (see Prognosis).
- Prognosis
Roughly half progress to ESKD within a decade: approximately 50% of patients with FSGS progress to ESKD within 10 years of diagnosis, rooted in low rates of treatment response.
- Prevention
Screen relatives of patients with a high-risk APOL1 genotype: offer APOL1 testing to first-degree relatives of a patient with biopsy-proven FSGS and a family history of ESKD; carriers warrant closer…
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