Rapidly Progressive Glomerulonephritis

Overview – Rapidly Progressive Glomerulonephritis

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome, not a separate disease, characterised by rapid loss of kidney function over days to weeks. It represents the aggressive progression of various underlying glomerular pathologies. Without prompt diagnosis and treatment, RPGN often leads to end-stage renal failure. The hallmark histological finding is crescent formation in glomeruli on kidney biopsy. Understanding its diverse causes is crucial for targeted management.

Definition

• RPGN is an aggressive form of glomerulonephritis that leads to renal failure within weeks to months.
• Defined by rapid decline in glomerular filtration rate (GFR) and characteristic crescentic glomerulonephritis on biopsy.

Aetiology

RPGN can arise from multiple underlying causes:

• Immune complex–mediated:
  • Post-streptococcal GN
  • Lupus nephritis
  • IgA nephropathy
• Anti-GBM antibody disease:
  • Goodpasture’s syndrome
• Pauci-immune/ANCA-associated:
  • Granulomatosis with polyangiitis (Wegener’s)
  • Microscopic polyangiitis
  • Eosinophilic granulomatosis with polyangiitis (Churg–Strauss)
• Idiopathic cases also occur

Pathophysiology

• Severe glomerular inflammation damages the glomerular basement membrane (GBM)
• Inflammatory mediators, fibrin, complement, and monocytes infiltrate Bowman’s space
• Parietal epithelial cell proliferation creates crescent-shaped lesions
• Crescents may undergo fibrosis, leading to permanent glomerular scarring

Clinical Features

• Features of nephritic syndrome:
  • Oliguria
  • Painless haematuria
  • Non-selective proteinuria
  • Oedema
  • Hypertension
• May present with rapid decline in renal function and systemic inflammatory signs

Investigations

• Renal biopsy:
  • Diagnostic gold standard
  • Crescentic glomeruli on light microscopy
  • Positive immunofluorescence depending on underlying cause
• Serology may guide underlying aetiology:
  • Anti-GBM antibodies
  • ANA, anti-dsDNA
  • ANCA (c-ANCA, p-ANCA)

Management

• Immunosuppressive therapy:
  • High-dose IV methylprednisolone (pulse therapy)
  • Oral corticosteroids (e.g. prednisone)
  • Cyclophosphamide or rituximab
• Plasmapheresis:
  • Especially in anti-GBM disease or severe ANCA-associated vasculitis
• Supportive care:
  • Dialysis if renal failure occurs
  • Consider renal transplant if irreversible ESRF

Complications

• End-stage renal failure (ESRF) – common if untreated or advanced at presentation
• Systemic vasculitis involvement (in ANCA-positive types)
• Pulmonary haemorrhage in Goodpasture’s syndrome

Differential Diagnosis

• Other causes of nephritic syndrome:
  • Post-streptococcal GN
  • IgA nephropathy
  • Lupus nephritis
  • Membranoproliferative GN
• Thrombotic microangiopathies (e.g. HUS, TTP)

Summary – Rapidly Progressive Glomerulonephritis

Rapidly progressive glomerulonephritis (RPGN) is a severe, rapidly evolving glomerular disease that leads to renal failure within weeks if untreated. It is a manifestation of various underlying disorders, including ANCA-associated vasculitis, lupus, or anti-GBM disease. Prompt immunosuppressive therapy and sometimes plasmapheresis are essential. For a broader context, see our Renal Overview page.