Rapidly Progressive Glomerulonephritis

Today we discussed a case of rapidly progressive glomerulonephritis (RPGN) secondary to granulomatosis with polyangiitis. What started as a very broad differential at the start of the case rapidly narrowed based on the active urinary sediment and progressive decline in renal function. Here is a way to think about RPGN:

Dysmorphic Red Cells in Urine. Courtesy of UpToDate

Dysmorphic Red Cells in Urine. Courtesy of UpToDate

Rapidly Progressive Glomerulonephritis (RPGN): A clinical syndrome of progressive acute to subacute decline in renal function and active urinary sediment (glomerular disease) resulting in crescentic glomerulonephritis.

  • Anti-GBM antibodies: (type IV collagen), Goodpasture’s syndrome
  • Pauci-Immune GN: necrotizing lesions within the glomeruli with few or no immune deposits
    • +ANCA: (systemic small-vessel vasculitis without immune deposition) 80%
      • Granulomatosis with polyangiitis (GPA, formerly known as Wegener granulomatosis)
        • +PR3-ANCA or c-ANCA
      • Microscopic polyangitis (MPA)
        • +MPO-ANCA or pANCA
      • Eosinophilic polyangiitis (EGPA, formerly known as Churg Strauss)
  • Immune Complex: immune complex deposition within the glomeruli
    • IgA Nephropathy
    • IgA Vasculitis (formerly known as Henoch-Schonelin Purpura)
    • Lupus Nephritis
    • Infection Related (anti-streptococcal antibodies)
    • MPGN
    • Cryoglobulinemia

Granulomatosis with polyangiitis (GPA):

  • Course: progresses slowly over months or explosively over days
  • Symptoms: constitutional symptoms including fever, malaise, anorexia, and weight loss in addition to arthralgias, rhinosinusitis, cough and dyspnea, active urine sediment with or without renal insufficiency, purpura, and neurologic dysfunction
    • In studies from the USA’s National Institutes of Health (NIH), glomerulonephritis was present in only 18 percent of patients at presentation
  • Diagnostics: +ANCA: 82-94% of patients with either GPA or MPA
    • GPA, MPA and EGPA are pathologically indistinguishable. Use history (asthma and eosinophilia with EGPA) and lab data to help distinguish (anti-PR3 with GPA vs. anti-MPO with MPA)