ANCA-mediated glomerulonephritis! 03/14/2019

Happy Pi Day!

Thanks to Brayden for presenting a case of a 48yo M with no significant medical or family history presenting with 2-3 months of LE edema, generalized weakness, malaise, myalgias, and arthralgias (general, no particular pattern). He was found to be anemic, and urine studies were notable for nephritic range proteinuria and microscopic hematuria. His complements levels were normal. Ultimately renal biopsy revealed the presence of crescents in the glomeruli, and MPO positivity indicating a P-ANCA related vasculitides. Based on his history, his final diagnosis is RPGN Type 3 secondary to most likely MPA.


Hematuria: First step is to see if there is actually RBC in the urine! 

  • With RBC
    • RBC Casts, proteinuria, AKI
      • Glomerular pathology
    • No casts, no AKI
      • Non-glomerular bleed
        • UTI
        • BPH
        • Renal cysts
        • Sickle Cell
        • Interstitial disease
        • Nephrolithiasis
        • Post exercise
        • Tumors
    • Without RBC
      • Porphyria, Beeturia, Rhabdomyolysis

All About Casts! Presence of certain casts in the urine can provide useful information.

  • Hyaline casts: Nephrotic syndrome, pre-renal azotemia, normal
  • Fatty oval bodies: Nephrotic syndrome
  • RBC casts: GN
  • Granular cast: ATN, interstitial nephritis, note that you can see ATN even without casts!
  • WBC cast: Interstitial nephritis, acute pyelonephritis, acute GN

Glomerulonephritis

  • Presentation
    • Glomerular inflammatory leading to hematuria, variable range proteinuria, HTN, edema, RBC casts or dysmorphic RBC
  • Etiology
    • Immune Complex Deposition GN
      • Typically LOW complement levels
      • Differential
        • SLE GN: ANA, DS-DNA
          • C3 way lower than C4
        • PIGN (post-infectious or strep GN, infection related GN): Streptococcal antibodies i.e. ASO, recent infection
          • Low C3, Low CH50, normal C4
          • Supportive care + antibiotics
          • Typically weeks after an infection but can occur during infection
        • IgA nephropathy: MOST COMMON, recent respiratory or GI infection, kidney biopsy with IgA deposits, normal complements
        • Cryglobulinemic GN: Cryoglobulin, HCV association
          • C4 way lower than C3
        • Membranoproliferative GN (MPGN): Complement activation, immune-staining positivity on biopsy
        • HSP (nrl complements), palpable purpura, abd pain. IgA, IgG, C3 deposition. Closely related to IgA Nephropathy but with systemic/extra-renal involvement.
        • Subacute bacterial endocarditis (Low C3, fever, + cultures)
        • Atheroembolism: + eosinophilia + eosinouria
    • Anti-GBM (Good Pastures) GN
      • NORMAL complement levels
      • Positive anti-GBM
      • Lung and renal involvement, young patients <30 are more likely to have involvement of both and older patients > 50 are more likely to present with isolated GN. Male predominance in younger patients and female predominance in older patients.
    • ANCA related GN aka Pauci-immune GN (PIGN)
      • NORMAL complement levels
      • Absent extra-renal disease: ANCA-associated crescentric GN
      • Systemic necrotizing vasculitis, P-ANCA/MPO: Microscopic polyangiitis (MPA)
      • Respiratory sx, sinusitis, granulomas, C-ANCA/PR3: Granulomatosis with polyangiitis (GPA)
      • Asthma and eosinophilia, P-ANCA/MPO: EGPA
      • Biopsy: None to few immune deposits in the glomeruli in IF and EM. 96% will be positive for ANCA, the other 4% are ANCA-negative pauci-immune GN
        • Focal necrotizing, crescentic glomeruli
    • RPGN: Rapid renal failure with extensive crescent formation that can lead to ESRD within weeks to months. Can present in any age group.
      • Association: Goodpasture, SLE, GPA, idiopathic
      • Complements: Nrl
      • Bx: Crescent formation in > 50-75% of glomeruli
      • IM: Linear IgG
      • Types: 3 types depending on immunofluorescence pattern.
        • Type 1: 20%, anti-GBM
        • Type 2: 25%, immune complex deposition, SLE, GSP, IgA nephropathy, acute proliferative GN
        • Type 3: Aka Pauci-immune GN, 55%, glomeruli damaged in unclear mechanism. Can be idiopathic or related to ANCA associated vasculitis like GPA, MPA, EPGA. Most common.
  • Diagnosis
    • Kidney biopsy for definitive diagnosis but it can be deferred if a diagnosis can be determined via serologies or if pts have fibrotic kidneys, which makes the risks for that diagnostic piece of information outweigh the benefits.
  • Management of GN:
    •  Treat underlying cause if any.
    • Immunosuppression: Usually high dose steroids + cyclophosphamide, rituximab may also be used. Plasmapheresis is also an option.
    • Initial therapy: Methyprednisolone 500-1000mg daily for 3 days
    • No different between use of rituxuimab vs cyclophosphamide (RAVE, RITUXVAS)
    • Cyclophosphamide: Available in PO formulation in a daily dosing, favored by some Nephrologist.
    • Prognosis
      • If left untreated, RPGN progresses to ESRD over weeks to months. Fewer crescents (<50%) is associated with slower progression.

Summary (souce: Grepmed)

GN

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