Rapidly progressive glomerulonephritis

1. Definition

• Rapid progressive loss of renal function over days to weeks.
• Untreated → acute renal failure & death.
• Manifests as oliguria/anuria + uremia + hematuria + proteinuria.

2. Common Histologic Feature — Crescents

• Severe capillary damage → fibrin escapes into Bowman space.
• Triggers proliferation of Bowman capsule parietal cells + macrophages → crescents.
• Crescent = ≥ 2 layers of proliferating cells in Bowman space.
• Hallmark of inflammatory GN and marker of severe glomerular injury.
• Crescents compress and obliterate glomerular capillaries.

3. Three Pathogenic Types of RPGN

Type I — Anti-GBM Antibody Crescentic GN

• Antibodies against GBM (target = collagen IV α3 chain, NC1 domain).
• IF: linear IgG along GBM.
• Antibody binding → GBM fragmentation → fibrinogen leak → crescents.
• Goodpasture syndrome: anti-GBM Abs cross-react with alveolar BM → lung + kidney involvement (hemoptysis + hematuria).
• Tx: plasmapheresis (plasma exchange) + immunosuppression → may help.

Type II — Immune Complex-Mediated Crescentic GN

• Complication of any IC-mediated GN:
  • Post-streptococcal GN
  • SLE nephritis
  • IgA nephropathy / HSP
  • Membranoproliferative GN
• IF: granular IC deposits (typically subepithelial).
• Tx: steroids can be useful; plasmapheresis less so.

Type III — Pauci-Immune Crescentic GN

• No anti-GBM Abs, no immune complexes.
• ANCA-positive vasculitis → cell damage.
• GBM fragmentation + segmental necrosis.
• Associated diseases:
  • Microscopic polyangiitis (MPO-ANCA / p-ANCA)
  • Granulomatosis with polyangiitis (Wegener; PR3-ANCA / c-ANCA)
  • Eosinophilic GPA (Churg-Strauss; p-ANCA)
• Tx: steroids + cyclophosphamide (or rituximab).

4. Comparison Table

Type	Type I	Type II	Type III
Mechanism	Anti-GBM Ab	Immune complex	Pauci-immune (ANCA)
IF pattern	Linear IgG	Granular IgG/C3	Negative
Classic disease	Goodpasture syndrome	Post-strep, SLE, IgA, MPGN	MPA, GPA (Wegener), Churg-Strauss
Serology	Anti-GBM Abs	Disease-specific (ANA, ASO, etc.)	c-ANCA / p-ANCA
Lung involvement	Yes (hemoptysis)	Rare	Common (GPA, Churg-Strauss)
Treatment	Plasmapheresis • immunosuppression	Treat underlying + steroids	Steroids + cyclophosphamide

5. Clinical Course

• Common to all: rapidly rising creatinine, oliguria/anuria, hematuria + RBC casts, proteinuria.
• Without prompt treatment → end-stage renal failure in weeks.
• Early recognition + treatment is critical.

💡 High-yield: RPGN = renal function loss in days–weeks + crescents (fibrin escape → Bowman capsule proliferation). Three types by IF: Type I linear (anti-GBM → Goodpasture, lung + kidney, Tx plasmapheresis); Type II granular (IC, post-strep / SLE / IgA, MPGN); Type III pauci-immune (ANCA: c-ANCA = GPA/Wegener, p-ANCA = MPA / Churg-Strauss, Tx steroids + cyclophosphamide). Crescents = histologic marker of severe glomerular injury.