RPGN
Summary
Rapidly Progressive Glomerulonephritis (RPGN) is a clinical syndrome characterized by acute loss of renal function over days to weeks, with histologic finding of crescents in >50% of glomeruli on biopsy. It represents a medical emergency requiring prompt diagnosis and treatment to prevent irreversible renal failure. RPGN is classified into three immunopathologic types: anti-GBM disease, immune complex-mediated, and pauci-immune (ANCA-associated).
Detail
RPGN is defined clinically by a rapid decline in GFR (rise in creatinine) over days to weeks, often accompanied by nephritic syndrome features (hematuria with dysmorphic RBCs, RBC casts, subnephrotic proteinuria, hypertension, edema). The pathologic hallmark is crescentic glomerulonephritis—crescent-shaped accumulations of proliferating cells (parietal epithelial cells, macrophages) and fibrin in Bowman's space, resulting from severe glomerular capillary wall injury that allows fibrinogen and inflammatory cells to leak into the urinary space.
RPGN is classified into three types based on immunofluorescence pattern:
1. Type I (Anti-GBM disease, ~20%): Linear IgG deposition along the GBM due to antibodies against type IV collagen (α3 chain of NC1 domain). Goodpasture syndrome occurs when anti-GBM antibodies cross-react with alveolar basement membrane, causing pulmonary hemorrhage plus RPGN.
2. Type II (Immune complex-mediated, ~40%): Granular ('lumpy-bumpy') IgG/C3 deposits from immune complex deposition. Causes include post-infectious GN, lupus nephritis (class III/IV), IgA nephropathy/Henoch-Schönlein purpura, and cryoglobulinemia. Complement levels often low.
3. Type III (Pauci-immune, ~40%): Little to no immune deposits on IF/EM ('pauci' = few). Associated with ANCA-associated vasculitis: granulomatosis with polyangiitis (c-ANCA/PR3), microscopic polyangiitis (p-ANCA/MPO), and eosinophilic granulomatosis with polyangiitis (Churg-Strauss).
Some sources describe a Type IV as a combination of anti-GBM and ANCA positivity.
Workup includes urinalysis (RBC casts, dysmorphic RBCs), serologies (anti-GBM antibodies, ANCA, ANA, anti-dsDNA, complement levels C3/C4, cryoglobulins), and renal biopsy—the gold standard for diagnosis, staging, and prognosis (percentage of crescents, degree of fibrosis).
Treatment is time-sensitive: high-dose corticosteroids plus cyclophosphamide or rituximab for immune-mediated causes. Plasmapheresis is added for anti-GBM disease (to remove circulating antibodies) and severe ANCA-associated disease with pulmonary hemorrhage or dialysis-dependence. Delay in treatment correlates with worse renal outcomes and progression to ESRD.
Sources
- Robbins and Cotran Pathologic Basis of Disease
- Harrison's Principles of Internal Medicine
- First Aid for the USMLE Step 1
- Brenner and Rector's The Kidney
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