FSGS is Nephrotic
Focal Segmental Glomerulosclerosis (FSGS) is definitively characterized as a nephrotic syndrome, not a nephritic syndrome. 1, 2
Clinical Classification
FSGS accounts for 7-20% of nephrotic syndrome cases in children and a significantly higher percentage in adults, with prevalence as high as 80% among nephrotic patients in Afro-Caribbean populations. 1
The disease presents with the classic features of nephrotic syndrome:
- Heavy proteinuria (≥3.5 g/day in adults; ≥1.0 g/m²/day in children) 2, 3
- Hypoalbuminemia (<3.0 g/dL in adults; <2.5 g/dL in children) 2, 3
- Edema 2, 3
- Hyperlipidemia (as a compensatory mechanism for protein loss) 2
Pathophysiological Mechanism
The underlying mechanism is podocyte dysfunction leading to increased glomerular permeability to proteins, which is the hallmark of nephrotic rather than nephritic disease. 2 A T-cell-driven circulating "glomerular permeability factor" interferes with glomerular permselectivity to albumin in FSGS. 2
This contrasts sharply with nephritic syndromes, which are characterized by glomerular inflammation, hematuria, hypertension, and acute kidney injury with minimal proteinuria.
Clinical Presentation Patterns
Adults with FSGS typically present with:
- Proteinuria (often nephrotic-range) 4, 5
- Microscopic hematuria (may be present but not the dominant feature) 4
- Hypertension 4
- Renal insufficiency 4
Patients with persistent nephrotic syndrome have more than 50% risk of progressing to end-stage renal disease within 5-10 years if untreated. 1 Those with proteinuria >3.8 g/day have a 35% risk of end-stage renal disease within 2 years. 2
Nephrotic Complications
FSGS patients experience typical nephrotic complications, not nephritic ones:
- Thromboembolism risk (29% for renal vein thrombosis, 17-28% for pulmonary embolism) due to loss of anticoagulant proteins 2
- Increased infection susceptibility due to loss of immunoglobulins and complement factors 2
- Hyperlipidemia requiring potential statin therapy 3
Common Pitfall
Do not confuse the presence of microscopic hematuria in FSGS with nephritic syndrome. 4 While hematuria can occur in FSGS, the dominant clinical picture is massive proteinuria with nephrotic-range losses, hypoalbuminemia, and edema—the defining features of nephrotic syndrome. The pathophysiology centers on podocyte injury and increased glomerular permeability, not inflammatory glomerular destruction as seen in nephritic syndromes.