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

Picture it — RPGN by immunofluorescence

CrescentFibrin and proliferating parietal cells fill Bowman space and squeeze the tuft.

Type I — anti-GBMLinear IgG along the GBM.

Type II — immune complexGranular, lumpy-bumpy deposits.

Type III — pauci-immuneLittle or no deposit; ANCA-positive.

Schematic diagrams, not to scale. Red = abnormal.

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