Clinicopathological Features and Outcomes of IgA Nephropathy with Serum Antineutrophil Cytoplasmic Autoantibody Positivity

<b><i>Introduction:</i></b> IgA nephropathy (IgAN) with serum antineutrophil cytoplasmic autoantibody (ANCA) positivity is uncommon. This study analyzed the clinicopathologic features and prognosis of IgAN patients with serum ANCA positivity. <b><i>Methods:</i></b> 2,864 IgAN patients were tested for ANCA by the indirect immunofluorescence assay and chemiluminescence immunoassay. Patients with serum ANCA positivity (<i>n</i> = 85) were identified, and their clinical, pathological, and prognostic characteristics were analyzed. They were compared with ANCA-negative IgAN patients (<i>n</i> = 170) and ANCA-associated systemic vasculitis (AAV) with renal involvement patients (<i>n</i> = 85) selected randomly. <b><i>Results:</i></b> 2.97% (85/2,864) of IgAN were ANCA positive, and 4 patients were diagnosed as having crescentic IgAN with ANCA positivity. The clinicopathological characteristics of ANCA-positive IgAN patients were comparable to ANCA-negative IgAN patients, but they had higher antinuclear antibody (ANA)-positive rates, lower levels of renal interstitial inflammation, and fewer immune depositions than ANCA-negative IgAN patients. Compared with AAV patients, ANCA-positive IgAN patients were younger and had fewer extrarenal manifestations, milder renal damage, and more immune complex depositions. The renal outcomes were similar between IgAN patients with and without ANCA positivity. Multivariate Cox analysis revealed that in IgAN patients with ANCA positivity, male, ANA positivity, higher serum creatinine and proteinuria, and more severe renal tubular atrophy/interstitial fibrosis were risk factors for adverse renal outcomes. <b><i>Conclusion:</i></b> The clinical, pathological features and prognosis of ANCA-positive IgAN patients were similar to those of ANCA-negative IgAN patients except for higher ANA-positive rate, milder renal inflammation, and fewer immune depositions. ANA positivity was an independent risk factor for adverse renal outcomes in ANCA-positive IgAN patients.