crescentic glomerulonephritis

Crescentic glomerulonephritis is a histopathologic pattern seen in several diseases that cause rapidly progressive glomerulonephritis (RPGN), defined clinically as loss of >50% renal function within days to weeks. Crescents form when severe glomerular capillary wall damage allows fibrin and plasma proteins to leak into Bowman's space, stimulating proliferation of parietal epithelial cells, macrophages, and fibroblasts, creating a crescent-shaped mass that compresses the glomerulus and obliterates the capillary tuft. If untreated, crescents progress from cellular to fibrocellular to fibrous, causing irreversible glomerulosclerosis.

Three major immunologic categories: 1. Type I (Anti-GBM disease): Antibodies against type IV collagen (alpha-3 chain) in the GBM. Linear IF pattern. Includes Goodpasture syndrome (with pulmonary hemorrhage). 2. Type II (Immune complex-mediated): Granular IF pattern. Caused by conditions like post-infectious GN, lupus nephritis, IgA nephropathy/Henoch-Schönlein purpura, and membranoproliferative GN progressing to crescents. 3. Type III (Pauci-immune): Little to no immune deposits on IF ("pauci" = few). Associated with ANCA-associated vasculitides: granulomatosis with polyangiitis (GPA, c-ANCA/PR3), microscopic polyangiitis (MPA, p-ANCA/MPO), and eosinophilic granulomatosis with polyangiitis (EGPA).

Clinical presentation: rapid decline in renal function, oliguria, hematuria with dysmorphic RBCs and RBC casts, proteinuria, hypertension, and edema. Systemic symptoms depend on underlying etiology (e.g., hemoptysis in Goodpasture, sinusitis/lung nodules in GPA).

Diagnosis requires renal biopsy showing crescents (typically >50% of glomeruli for RPGN diagnosis) plus immunofluorescence pattern to determine subtype. Serologic testing includes anti-GBM antibodies, ANCA (c-ANCA/PR3, p-ANCA/MPO), complement levels, and ANA/anti-dsDNA if lupus suspected.

Treatment is urgent and includes high-dose corticosteroids plus cyclophosphamide or rituximab for immunosuppression; plasmapheresis is added for anti-GBM disease and severe ANCA-associated disease to remove circulating antibodies. Early treatment is critical since prognosis correlates with the percentage of glomeruli involved and promptness of intervention—delay often leads to irreversible renal failure requiring dialysis or transplantation.