Can antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis cause secondary focal segmental glomerulosclerosis (FSGS)?

ANCA Vasculitis Does Not Cause Primary FSGS, But Can Present With Focal Global Glomerulosclerosis

ANCA-associated vasculitis does not cause focal segmental glomerulosclerosis (FSGS) as a primary disease pattern. The characteristic kidney lesion in ANCA vasculitis is pauci-immune necrotizing and crescentic glomerulonephritis, not FSGS 1, 2, 3.

Understanding the Distinction

Primary Pattern of ANCA Vasculitis

• The hallmark renal pathology is pauci-immune focal and segmental necrotizing and crescentic glomerulonephritis (NCGN), not FSGS 2, 3
• This presents with glomerular necrosis, cellular crescents, and minimal immune complex deposition on immunofluorescence 3, 4
• The pattern is characterized by active inflammatory injury rather than the podocyte injury and scarring seen in primary FSGS 1

Focal Global Glomerulosclerosis vs. FSGS

The confusion may arise from terminology, but these are distinct entities:

• Focal global glomerulosclerosis refers to completely scarred glomeruli and is listed as an "additional feature" in ANCA GN, representing chronic damage from prior inflammation 1
• The Mayo Clinic/Renal Pathology Society consensus shows ANCA GN can have focal global glomerulosclerosis (10-40% of glomeruli) as a secondary chronic finding 1
• This is fundamentally different from primary FSGS, which shows segmental sclerosis within individual glomeruli with podocyte foot process effacement 1

Clinical Implications

What You Actually See on Biopsy

When evaluating a kidney biopsy in ANCA vasculitis:

• Primary diagnosis: ANCA GN (MPO-ANCA or PR3-ANCA) 1
• Pattern of injury: Necrotizing and crescentic GN 1
• Additional features: May include focal global glomerulosclerosis representing chronic scarring from previous inflammation 1
• The histopathologic classification focuses on the percentage of normal glomeruli, crescentic glomeruli, and globally sclerotic glomeruli 1

Rare Case Report Exception

• One isolated case report from 1996 described ANCA positivity in a patient with FSGS on biopsy 5
• However, this represents either coincidental ANCA positivity or possible secondary vasculitis complicating immune complex disease, not ANCA vasculitis causing FSGS 5
• This single low-quality report does not establish a causal relationship and contradicts the established pathologic classification 1

Key Pitfall to Avoid

Do not confuse "focal global glomerulosclerosis" (completely scarred glomeruli) with "focal segmental glomerulosclerosis" (FSGS - segmental scarring within glomeruli). These are entirely different pathologic entities with different clinical implications 1. The former is a chronic sequela of many glomerular diseases including ANCA vasculitis, while the latter is a specific podocytopathy.