7. Rapidly progressive glomerulonephritis

Question 1

What is RPGN?

Answer 1

• It is a clinical syndrome without a specific etiologic form of GN.
• It is characterized by:
  
  • Rapid and progressive loss of renal function
  • Lab findings typical of nephritic syndrome
  • Often severe oliguria
  • Often systemic symptoms of vasculitis
• If untreated it leads to death from renal failure within a period of days to months

Question 2

What is the etiology and pathophysiology of RPGN?

Answer 2

• Characteristic histological finding: presence of crescents (crescenteric GN)
• May be cause by a number of different diseases. Some restricted to the kidney and some systemic
• In most cases, the glomerular injury is immunologically mediated:
  
  • 12% of patients have anti-GBM antibody-mediated GN with or without lung involvement
  • 44% have immune complex GN with crescents
  • 44% have pauci immune crescenteric GN

Question 3

What is ant-GBM antibody-mediated crescenteric GN?

Answer 3

• It is characterized by linear deposits of IgG and, in many cases, C3 on the glomerular basement membrane
• In some patients, anti-GBM antibodies are found on the pulmonary alveolar-capillary basement membranes ==> pulmonary hemorrhage associated with renal failure (Goodpasture’s syndrome)
• Anti-GBM antibodies are found in the serum and are useful for diagnosis
  
  • This allows plasmapheresis to be done ==> removal of pathogenic antibodies from circulation

Question 4

What is immune complex-mediated crescenteric GN?

Answer 4

• Crescents can be complications of any immune complex nephritis, including:
  
  • Post-strep GN
  • SLE
  • IgA nephropathy
  • Henoch-schönlein purpura
• These disorders usually don’t respond to plasmapheresis

Question 5

What is Pauci-immune crescenteric GN?

Answer 5

• Defined by the lack of anti-GBM antbodies or significant immune complex deposition detectable by immunofluorescence and electron microscopy
• ANCA (antineutrophil cytoplasmic antibodies) are typically found in the serum, which has pathogenic role in some vasculitides
  
  • Thus, sometimes, crescenteric GN is part of a systemic vasculitis (e.g. microscopic polyangitis or Wegener granulomatosis)
• In many cases, Pauci-immune crescenteric GN is limited to the kidney and is thus idiopathic

Question 6

What are the clinical features of RPGN?

Answer 6

• AKI
• Possible systemic features:
  
  • Fever, myalgia, weight loss, hemoptosis
• Pulmonary hemorrhage (most common cause of death in ANCA positive patients)

Question 7

What is the treatment of RPGN?

Answer 7

• Aggressive immunosuppression with high dose IV steroids and cyclophosphamides
• Some patients benefit from plasmapheresis (anti-GBM mediated RPGN)

Question 8

What is the prognosis of RPGN?

Answer 8

• 5-year survival is 80%
• It is roughly related to the fraction of involved glomeruli
  
  • Patients in whom crescents are present in < 80% of glomeruli ==> better prognosis that those in whom the percentage of crescents is > 80%.