Crescentic Glomerulonephritis (GN) with Anti-glomerular Basement Membrane (GBM) Antibodies and ANCA: Double Trouble

Introduction: Crescentic GN is characterized by rapid deterioration of kidney function and is caused by antibodies against glomerular basement membrane (anti-GBM), immune complex or pauci-immune etiologies. We present a case of RPGN with anti-GBM Ab and Myeloperoxidase (MPO)-ANCA positivity. Case Description: 37-year-old male with no prior medical history presented with abdominal pain, hematuria and oliguria. On admission, serum creatinine was 19.72 mg/dL and potassium 7.3 mEq/L. Urine with protein >500 mg/dL and hematuria. Hemodialysis(HD) was started for metabolic abnormalities. Serologies revealed ANA positive, MPO >8units, GBM-Ab >8units, and P-ANCA titer >1:640. Kidney biopsy was obtained after 3 sessions of HD and 10 days after presentation. Biopsy revealed 39/49 glomeruli with circumferential cellular crescents (fig 1) as well as necrotizing arteritis. Immunofluorescence showed GBM linear positivity with IgG 3+ (fig 2), kappa 3+, lambda 3+ and C3 3+. Electron microscopy showed breaks in GBM, and no immune complexes seen. He was transferred to our hospital for further management. Course was complicated by hemoptysis and retroperitoneal hematoma requiring embolization of left renal artery pseudoaneurysm. Steroid induction was promptly started. After stabilization, he received 18 sessions of plasmapheresis and oral Cytoxan 1 mg/kg daily with steroid taper resulting in a drop in anti-GBM Ab to 1.8units. He remains dialysis dependent. Discussion: Anti-GBM Ab and ANCA associated GNs are rare, but approximately 20%-30% of patients with anti-GBM disease have MPO antibodies. Dual antibody positivity has a worse renal prognosis compared to patients with ANCA related GN. Patient survival is worse in those presenting with acute renal failure requiring dialysis. Our patient’s age is much lower than the mean age of presentation for double positive cases. Prompt treatment needs to be started without waiting for biopsy due to fulminant nature of anti-GBM disease followed by longer maintenance therapy due to relapsing nature of ANCA disease.Figure 1(fibro cellular crescent), figure 2(linear pattern of anti GBM antibodies)