The Silent Catastrophe: Isolated Renal Collapse in Double Positive Anti-GBM and Myeloperoxidase (MPO)-ANCA-Associated Disease

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune condition, approximately 20–40% of anti-GBM cases exhibit "double positivity" (DPPs), with concurrent anti-GBM and ANCA antibodies. We describe a 60-year-old male with double positive anti-GBM and MPO-ANCA antibodies presenting with isolated renal involvement. Case Description: A 60-year-old male with hypertension, hyperlipidemia, obesity, and a 20-pack-year smoking history presented with nausea, vomiting, and dark brown urine over three weeks. He reported decreased urine output but denied systemic symptoms such as rash, joint pain, or hemoptysis. On admission, he exhibited non-oliguric acute kidney injury (AKI) and uremia. Urinalysis revealed non-nephrotic proteinuria (UPCR 1.5 g), dysmorphic RBCs, and RBC casts. Serologic testing showed positive p-ANCA (1:40), anti-MPO >8, and anti-GBM >8. Renal biopsy demonstrated crescentic glomerulonephritis in 75% of glomeruli, linear IgG staining on immunofluorescence, and thickened glomerular basement membranes without immune complex deposition on electron microscopy. The Birmingham Vasculitis Activity Score (BVAS) was 12. Treatment included high-dose intravenous methylprednisolone with taper, plasmapheresis for 14 days, and rituximab. Rituximab was chosen over cyclophosphamide after shared decision-making due to concerns about myelosuppression and was administered weekly for four weeks. Despite timely intervention, renal function deteriorated further, and the patient remained dialysis-dependent and on oral steroids at discharge and at three-month follow-up. Discussion: DPPs disease is a rare and life-threatening autoimmune vasculitis with or without pulmonary involvement. Diagnosis is established through serologic markers, histopathology, and clinical presentation. Poor prognostic indicators include >85% crescentic involvement and the potential for relapse driven by ANCA-mediated vasculitis. Standard treatment involves a combination of plasmapheresis, corticosteroids, and cyclophosphamide. Rituximab, while increasingly used in ANCA-associated vasculitis, has limited data supporting its efficacy in primary induction for DPPs. Unlike isolated anti-GBM disease, DPPs require long-term immunosuppression to prevent relapse.