Unveiling the Uncommon: ANCA-Positive IgA Nephropathy

Introduction: Occurrence of antineutrophilic cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) with immunoglobulin A nephropathy (IgAN) is infrequent. Circulating ANCAs have an underlying role in pathogenesis of this combined entity. We report a rare case of new-onset AAV in a 68-year-old male with IgAN, presenting years after the initial diagnosis of IgAN. Case Description: A 68-year-old male with stable IgAN was evaluated for epistaxis, hematuria, and purpuric rash over lower extremities occurring over two months. Workup revealed dysmorphic urinary red blood cells, proteinuria, and elevated creatinine (Cr) to 2.62 mg/dl. He also had significantly elevated inflammatory markers and ANCA titers. A repeat kidney biopsy showed fibrinoid necrosis with cellular crescents. Immunofluorescence demonstrated 3+ mesangial IgA deposits. This combination of positive ANCA titers, systemic symptoms, and fibrinoid necrosis provided compelling evidence for a new ANCA-mediated vasculitic process superimposed on IgAN. Intensive corticosteroid therapy was initiated. He then developed an acute diarrheal illness leading to worsening renal failure (BUN/Cr: 243/8.4). Due to rapidly progressive renal failure, cyclophosphamide was started. Plasmapheresis and hemodialysis were eventually required due to minimal renal recovery. Discussion: Hallmark of ANCA-associated glomerulonephritis is fibrinoid necrosis of the small vessels. ANCA-positive IgAN patients commonly present with extrarenal symptoms as compared to the ANCA-negative IgAN group. Immunotherapy improves renal outcomes and vasculitic symptoms and lowers ANCA titers. It does not reduce the risk of progression to dialysis. Severe proteinuria, advanced age, and low initial eGFR are markers of poor prognosis. IgAN requires regular monitoring of Cr, proteinuria, and changes in symptoms. ANCAs are reported in less than 2% of IgAN patients and may be present during active disease or appear later. ANCAs are pathogenic and not merely biomarkers of AAV. Epitope specificity influences their pathogenicity. These patients have a challenging clinical course. To prevent diagnostic pitfalls, it is essential to repeat kidney biopsy for prompt diagnosis and treatment of ANCA-positive IgAN.