Rapidly progressive glomerulonephritis (RPGN)

Definition

Rapidly progressive glomerulonephritis (RPGN) is an acute nephritic syndrome that progresses to kidney failure within weeks to months. Histologically it is defined by crescent formation (extracapillary proliferation) in more than 50% of glomeruli, making it a pathologic diagnosis.

Classification

Immunofluorescence types

Classification is based on the immunofluorescence pattern and serology:

• Type I – anti-GBM antibody-mediated: linear IgG deposition along the basement membrane; called Goodpasture syndrome when pulmonary hemorrhage is present
• Type II – immune complex-mediated: granular deposits; e.g. postinfectious glomerulonephritis, endocarditis, lupus nephritis, IgA vasculitis, IgA nephropathy, cryoglobulinemia, membranoproliferative glomerulonephritis
• Type III – pauci-immune: no or scant immune deposits; almost always ANCA-positive (PR3- or MPO-ANCA) in granulomatosis with polyangiitis, microscopic polyangiitis or renal-limited vasculitis
• Double-antibody positive form: anti-GBM antibodies and ANCA at the same time; rare

Aetiopathogenesis

The common final pathway is severe inflammatory damage to the glomerular capillaries. Epithelial cells then proliferate in Bowman space, often interspersed with neutrophils, and form crescents that fill the capsular space and compress the capillary tuft. Reported frequencies of the individual types vary between cohorts.

Clinical features

Onset is often insidious with weakness, fatigue, fever, nausea, vomiting, anorexia, joint and abdominal pain. About half of patients have edema and report a flu-like illness in the 4 weeks before kidney failure, followed by severe oliguria. Some cases begin like postinfectious glomerulonephritis with sudden hematuria. Hypertension is uncommon and rarely severe. In anti-GBM disease and ANCA vasculitis, pulmonary hemorrhage with hemoptysis or diffuse infiltrates may occur (pulmonary-renal syndrome).

Histology

Cellular crescents of proliferating epithelial cells, often with neutrophils, fill Bowman space in more than 50% of glomeruli; the capillary tuft is usually hypocellular and collapsed. Fibrinoid necrosis in the tuft or crescent points to vasculitis. Immunofluorescence distinguishes linear (anti-GBM), granular (immune complex) and negative (pauci-immune) patterns.

Diagnosis

• Kidney function: creatinine almost always elevated and rising rapidly
• Urine: hematuria always, usually red blood cell casts and dysmorphic red cells; often a "telescopic" sediment with white cells and red cell, white cell, granular and waxy casts
• Blood count: usually anemia, often leukocytosis
• Serology: anti-GBM antibodies (type I); antistreptolysin O, anti-DNA antibodies, cryoglobulins and C3 and C4 (type II, hypocomplementemia common); ANCA (type III)
• Early kidney biopsy: confirms the diagnosis and determines the type

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Rapidly Progressive Glomerulonephritis (RPGN)
2. MSD Manual Professional: Acute Kidney Injury (AKI)

Cross-references