STEPTRACKERRENAL | PATHOLOGY + IMMUNOLOGY + PHARMACOLOGY | HIGH-YIELD REVIEW

Nephritic Syndrome II — Rapidly Progressive GN

Glomeruli lose function within weeks as crescents fill Bowman space — sorted by what immunofluorescence shows.

FOCUS ON
Crescents = fibrin + macrophages + parietal epithelial cells → kidney failure in weeks. Linear IF = anti-GBM (Goodpasture: lungs + kidneys). Granular IF = immune complex (PSGN, lupus, IgA, MPGN). Negative IF = pauci-immune ANCA disease: GPA (PR3), microscopic polyangiitis (MPO), EGPA (MPO, asthma, eosinophils).
DISEASE
MECHANISM
FINDINGS
CLUE · TREATMENT
Crescent formation
Severe injury ruptures the GBM → fibrin and plasma proteins (C3b) leak into Bowman space
Parietal epithelial cells, monocytes, macrophages proliferate → crescent → fibrosis
Rapid creatinine rise over weeks
Type I — anti-GBM disease
Type II hypersensitivity: antibodies to the α3 chain of type IV collagen
Linear IgG along GBM; crescents
Plasmapheresis + steroids + cyclophosphamide
Goodpasture syndrome
Same antibody attacks alveolar basement membrane
Hemoptysis + hematuria; young men; smoking, inhaled hydrocarbons unmask antigen
Bimodal: young men, older women
Type II — immune complex RPGN
Severe immune complex GN
Granular IF; PSGN, diffuse proliferative lupus, IgA nephropathy/vasculitis, MPGN, cryoglobulinemia
Low C3 in most (not IgA)
Type III — pauci-immune RPGN
ANCA activate neutrophils → necrotizing small-vessel vasculitis
No immune deposits on IF; crescents, fibrinoid necrosis
Normal complement · steroids + rituximab or cyclophosphamide
Granulomatosis with polyangiitis
PR3-ANCA (c-ANCA); necrotizing granulomas + vasculitis
Upper airway (sinusitis, saddle nose, otitis), lungs (nodules, cavities, hemoptysis), kidneys (RPGN)
Classic triad: ENT, lung, kidney
Microscopic polyangiitis
MPO-ANCA (p-ANCA); vasculitis without granulomas
Lungs (alveolar hemorrhage) and kidneys; no nasopharyngeal disease
Palpable purpura
Eosinophilic granulomatosis with polyangiitis
MPO-ANCA in ~40%; eosinophil-rich granulomas
Asthma, sinusitis, eosinophilia, mononeuritis multiplex; kidney less often
↑ IgE · steroids, mepolizumab
Drug-induced ANCA vasculitis
Drugs trigger MPO-ANCA
Hydralazine, propylthiouracil, levamisole-contaminated cocaine, minocycline
Stop the drug
Pulmonary-renal syndromes
Alveolar hemorrhage + GN
Anti-GBM, GPA, MPA, SLE
Check anti-GBM, ANCA, ANA, complement

Mechanism — crescent building

Antibody, complexes or ANCA
→
Capillary wall necrosisGBM breaks
→
Fibrin into Bowman space
→
Cellular crescentParietal cells + macrophages
→
Fibrous crescentGlomerulus lost

Treat during the cellular crescent stage — fibrous crescents don't recover.

Reading the immunofluorescence

PATTERN
MEANING
EXAMPLES
Linear IgG
Antibody to GBM itself
Anti-GBM / Goodpasture
Granular
Immune complexes
PSGN, lupus, MPGN, cryo
Mesangial IgA
IgA complexes
IgA nephropathy, IgA vasculitis
Negative
No deposits — ANCA
GPA, MPA, EGPA
Linear but not anti-GBM
Diabetic nephropathy can show linear IgG (nonspecific trapping) — no crescents, no anti-GBM antibody.

How it's tested

COMMON CONFUSIONGoodpasture and GPA both cause hemoptysis with hematuria. Linear IF and anti-GBM antibody = Goodpasture; sinus disease, PR3-ANCA and negative IF = GPA.
THE TRAPNormal complement does not rule out RPGN. Anti-GBM and ANCA vasculitis both have normal C3 — only immune complex RPGN lowers it.
YOUR APPROACHRapid creatinine rise + nephritic urine → biopsy IF pattern → serology (anti-GBM, ANCA type, complement) → extra-renal organs → urgent immunosuppression ± plasmapheresis.

If you see… think…

Young smoker with hemoptysis, hematuria, linear IgG → Goodpasture syndrome
Antigen in Goodpasture → α3 chain of type IV collagen
Saddle nose, sinusitis, lung cavities, RBC casts, PR3-ANCA → GPA
Alveolar hemorrhage + RPGN, MPO-ANCA, no ENT disease → microscopic polyangiitis
Asthma, eosinophilia, foot drop, p-ANCA → EGPA
Crescents with no immune deposits → pauci-immune (ANCA) GN
Crescents with granular deposits and low C3 → immune complex RPGN
MPO-ANCA vasculitis on hydralazine → drug-induced ANCA vasculitis
Treatment for anti-GBM disease that removes antibody → plasmapheresis
Cells forming the crescent → parietal epithelial cells + macrophages