Abstract
INTRODUCTION: Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is a rare, complex autoimmune condition. Although ANCAs have a pathogenic role, they are considered a suboptimal biomarker of disease activity. Previous studies suggest differences in clinical phenotypes and outcomes in those without detectable circulating autoantibody. This study aimed to investigate the clinical presentation, histopathological findings, treatment practices, and outcomes of patients with ANCA-negative pauci-immune glomerulonephritis (PIGN). METHODS: A retrospective, multicenter cohort study was conducted from 2002 to 2022 and included those with biopsy-proven PIGN. We aimed to investigate differences in presentation, clinical outcomes, and treatment practices of patients with ANCA-negative PIGN when compared with ANCA-positive controls. RESULTS: In total, 132 ANCA-negative and 127 ANCA-positive patients were included. ANCA-negative patients were younger (P < 0.001), more commonly presented with renal-limited disease (P < 0.001), had worse estimated glomerular filtration rate at diagnosis (P < 0.02) and higher rates of proteinuria (P < 0.01). Controlling for age, sex, ethnicity, and recruiting center, ANCA-negative patients had lower rates of relapse (P < 0.001) and higher rates of end-stage kidney disease (ESKD) at 1 and 3 years (P < 0.001). Standard remission induction and maintenance therapies were used less often in ANCA-negative patients. CONCLUSION: The precise pathophysiology and factors contributing to the clinical phenotype of ANCA-negative PIGN remain unclear and potentially represent a distinct disease entity. Adverse outcomes may result from delays in diagnosis, advanced disease at presentation, and less intense immunosuppressive treatment. Current classification criteria inadequately address ANCA-negative disease and collaborative research, which includes ANCA-negative patients in trials is needed.