Renal · Year 2 · from Renal

Case 3: ANCA-Associated Glomerulonephritis

Patient Presentation

Demographics: 68-year-old female

Chief Complaint: Blood in urine, fatigue, and shortness of breath for 2 weeks

History of Present Illness: The patient noticed cola-colored urine 2 weeks ago along with progressive fatigue and dyspnea on exertion. She has had low-grade fevers, joint pains, and a 5-pound weight loss. She also reports a several-month history of recurrent sinusitis and epistaxis. No recent infections or medication changes.

Physical Examination:

  • Blood pressure: 162/96 mmHg
  • Heart rate: 88 bpm
  • Temperature: 37.8C
  • General: Ill-appearing
  • HEENT: Nasal crusting, saddle nose deformity
  • Lungs: Bibasilar crackles
  • Skin: Palpable purpura on lower extremities
  • Extremities: 1+ edema

Workup and Results

Laboratory Studies:

  • Creatinine: 4.8 mg/dL (baseline 0.9 three months ago)
  • BUN: 68 mg/dL
  • Hemoglobin: 9.2 g/dL
  • Urinalysis: 3+ blood, 2+ protein, RBC casts, dysmorphic RBCs
  • 24-hour urine protein: 2.1 g
  • c-ANCA (PR3): Strongly positive
  • p-ANCA (MPO): Negative
  • C3 and C4: Normal
  • Anti-GBM antibody: Negative

Chest X-ray:

  • Bilateral pulmonary infiltrates concerning for hemorrhage

Renal Biopsy:

  • Light microscopy: Crescentic glomerulonephritis (>50% crescents)
  • Immunofluorescence: Pauci-immune (minimal to no staining)
  • Electron microscopy: No immune deposits

Clinical Image

Renal biopsy demonstrating crescentic glomerulonephritis with cellular crescent formation (arrow) compressing the glomerular tuft. The pauci-immune pattern on immunofluorescence is characteristic of ANCA-associated vasculitis.

Diagnosis

Granulomatosis with Polyangiitis (GPA) with Rapidly Progressive Glomerulonephritis

  • c-ANCA/PR3 positive (associated with GPA)
  • Pulmonary-renal syndrome
  • Upper respiratory involvement (sinusitis, saddle nose)
  • Pauci-immune crescentic GN

Discussion

This case illustrates ANCA-associated vasculitis:

  • RPGN Type III: The lecture classifies RPGN by immunofluorescence pattern. Type III is pauci-immune (negative or minimal staining) and ANCA-associated. Types I (linear, anti-GBM) and II (granular, immune complex) have different mechanisms.
  • c-ANCA and PR3: The lecture notes that c-ANCA targeting proteinase-3 (PR3) is most associated with granulomatosis with polyangiitis (formerly Wegener's). p-ANCA/MPO is associated with microscopic polyangiitis.
  • Crescent Formation: Crescents form when inflammatory cells breach Bowman's capsule. More than 50% crescents indicates severe disease requiring urgent treatment.
  • Pulmonary-Renal Syndrome: Concurrent lung and kidney involvement should prompt consideration of anti-GBM disease and ANCA vasculitis.

Treatment Plan

  1. Induction Therapy:
  • Pulse methylprednisolone (500-1000 mg IV daily x 3 days)
  • Rituximab OR cyclophosphamide
  • Consider plasma exchange for severe disease (creatinine >5.7 or pulmonary hemorrhage)
  1. Maintenance Therapy:
  • Rituximab OR azathioprine
  • Low-dose prednisone taper
  1. Supportive Care:
  • PCP prophylaxis (TMP-SMX)
  • Blood pressure control
  • May require temporary dialysis
  1. Monitoring:
  • ANCA titers (rising may predict relapse)
  • Renal function
  • Watch for treatment-related infections

Teaching Points

  1. RPGN requires urgent diagnosis and treatment to preserve renal function
  2. c-ANCA/PR3 is associated with GPA; p-ANCA/MPO with microscopic polyangiitis
  3. Pauci-immune pattern on IF indicates ANCA-associated vasculitis
  4. The classic triad of GPA involves upper respiratory, lower respiratory, and kidney

Image Reference

For visual reference of glomerular disease concepts, see:

Learning Points

  1. Nephrotic vs Nephritic: Nephrotic features heavy proteinuria, hypoalbuminemia, edema; nephritic features hematuria, RBC casts, hypertension, mild proteinuria
  1. MCD Responds to Steroids: 90% of minimal change disease achieves complete remission with corticosteroids
  1. Anti-PLA2R for Membranous: 70% of primary membranous nephropathy is anti-PLA2R positive
  1. Thrombosis in Nephrotic: Membranous nephropathy has highest thrombosis risk; anticoagulate if albumin <2.5 g/dL
  1. ANCA Patterns: c-ANCA/PR3 = GPA; p-ANCA/MPO = MPA; both cause pauci-immune crescentic GN

All cases for this lecture as Markdown