What is the clinical presentation of Rapidly Progressive Glomerulonephritis (RPGN)?

Clinical Presentation of Rapidly Progressive Glomerulonephritis (RPGN)

Rapidly Progressive Glomerulonephritis (RPGN) presents as a severe clinical syndrome characterized by rapid decline in kidney function over days to weeks that leads to irreversible kidney failure if not diagnosed and treated promptly. 1 The clinical presentation includes specific symptoms, laboratory findings, and pathological features that help in early recognition and management.

Key Clinical Features

Symptoms and Signs

• Hematuria (often tea-colored or "cola-colored" urine)
• Oliguria (decreased urine output)
• Edema (peripheral and/or periorbital)
• Hypertension
• Fatigue
• "Flu-like syndrome" (early non-specific manifestation) 2
• Shortness of breath (in cases with pulmonary involvement)
• Hemoptysis (especially in anti-GBM disease or ANCA vasculitis with pulmonary involvement) 3
• Rash (in systemic vasculitis or lupus nephritis)

Laboratory Findings

• Elevated serum creatinine with rapidly declining eGFR
• Active urinary sediment with:
  • Red blood cell casts
  • Dysmorphic red blood cells
  • White blood cells
• Proteinuria (typically non-nephrotic but can be in nephrotic range)
• Hypocomplementemia (in immune complex-mediated RPGN)
• Positive serological markers:
  • ANCA (anti-MPO or anti-PR3) in pauci-immune RPGN
  • Anti-GBM antibodies in Goodpasture's disease
  • ANA and anti-dsDNA in lupus nephritis 1

Pathological Classification

RPGN can be classified into three major immunopathological categories:

1. Type I: Anti-GBM antibody disease (Goodpasture's syndrome)

   • Linear IgG deposits along the glomerular basement membrane
   • Often associated with pulmonary hemorrhage

2. Type II: Immune complex-mediated RPGN

   • Granular immune deposits in glomeruli
   • Causes include:
     • Lupus nephritis
     • Post-infectious glomerulonephritis
     • IgA nephropathy
     • Membranoproliferative glomerulonephritis

3. Type III: Pauci-immune RPGN

   • Few or no immune deposits
   • Most commonly associated with ANCA-positive vasculitis (>50% of RPGN cases)
   • Includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) 1, 3

Histopathological Features

The hallmark histopathological finding in RPGN is:

• Crescentic glomerulonephritis with crescents in ≥50% of glomeruli 3
• Crescents represent extracapillary proliferation of cells and matrix
• May be cellular, fibrocellular, or fibrous depending on the stage
• Often accompanied by fibrinoid necrosis of the glomerular tuft 3

Diagnostic Approach

1. Urinalysis and microscopy

   • Active urinary sediment with RBC casts is highly suggestive of RPGN

2. Serological testing

   • ANCA (anti-MPO and anti-PR3)
   • Anti-GBM antibodies
   • Complement levels (C3 and C4)
   • ANA and anti-dsDNA
   • Hepatitis serologies
   • Cryoglobulins 1

3. Kidney biopsy

   • Gold standard for definitive diagnosis
   • Essential for determining the specific type of RPGN
   • Provides prognostic information based on the percentage of crescents and chronicity 1

Important Clinical Considerations

• RPGN is a medical emergency requiring prompt diagnosis and treatment
• In patients with clinical features of RPGN and positive ANCA or anti-GBM antibodies, treatment should not be delayed while waiting for kidney biopsy results 3, 1
• Early recognition and treatment significantly improve outcomes and can prevent progression to end-stage kidney disease 2
• The presence of fibrous crescents and significant chronicity on biopsy indicates poor prognosis 4

Early recognition of even seemingly non-specific manifestations like "flu-like syndrome" with glomerular hematuria is crucial, as these may be present before the rapid decline in kidney function becomes evident 2.