Causes of Rapidly Progressive Glomerulonephritis (RPGN)
RPGN is caused by three major pathologic categories: ANCA-associated vasculitis (the most common cause), anti-GBM antibody disease, and immune complex-mediated glomerulonephritis. 1, 2
Primary Etiologic Categories
1. Pauci-Immune RPGN (ANCA-Associated Vasculitis)
This is the most common cause of RPGN, accounting for approximately 50-60% of cases. 2, 3, 4
- Granulomatosis with polyangiitis (GPA) - characterized by necrotizing inflammation of small vessels with granulomatous inflammation, typically PR3-ANCA positive 1
- Microscopic polyangiitis (MPA) - small-vessel vasculitis without granulomatous inflammation, typically MPO-ANCA positive 1
- Eosinophilic granulomatosis with polyangiitis (EGPA) - less commonly presents as RPGN 1
Approximately 90% of patients with pauci-immune RPGN have detectable ANCA antibodies (MPO or PR3), though ANCA negativity does not exclude the diagnosis. 1, 3
2. Anti-GBM Antibody Disease (Goodpasture's Syndrome)
This accounts for approximately 20% of RPGN cases. 2, 5
- Characterized by circulating anti-glomerular basement membrane antibodies 1, 2
- Often presents with pulmonary-renal syndrome (simultaneous lung and kidney injury) 1
- Some patients have both ANCA and anti-GBM antibodies (double-positive disease) 1
3. Immune Complex-Mediated RPGN
This category accounts for approximately 20-25% of RPGN cases. 5, 6
- IgA nephropathy with extensive crescent formation (usually >50% of glomeruli) with concomitant rapid GFR decline 1
- IgA vasculitis nephropathy (Henoch-Schönlein purpura) with RPGN pattern 1
- Lupus nephritis with crescentic features 6
- Post-infectious glomerulonephritis (particularly in children, though typically has better prognosis) 6
- Membranoproliferative glomerulonephritis 6
Critical Diagnostic Distinction
The presence of crescents alone on kidney biopsy without a concomitant rapid decline in GFR does not constitute RPGN - true RPGN requires both histologic crescents AND rapid deterioration of kidney function over days to weeks. 1, 2
Common Clinical Pitfall
Do not delay immunosuppressive therapy while waiting for kidney biopsy results if clinical presentation is compatible with small-vessel vasculitis and MPO- or PR3-ANCA serology is positive, especially in rapidly deteriorating patients. 1 However, infection must be excluded before initiating significant immunosuppression. 2