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. 2025 Mar 3;10(5):1450-1459.
doi: 10.1016/j.ekir.2025.02.032. eCollection 2025 May.

Clinical Presentation and Outcomes of Antineutrophil Cytoplasmic Autoantibody-Negative Pauci-Immune Glomerulonephritis

Lauren Floyd  1   2 , Anamay Shetty  3 , Adam D Morris  2 , Krešimir Galešić  4 , Mohamed Elsayed  2 , Grace Lavery  2 , Amrita Dhutia  5 , Sorcha O'Brien  6 , Sinead Stoneman  7 , Allyson Egan  8 , Mark A Little  6 , Vojtech Kratky  9 , Zdenka Hruskova  9 , Vladimir Tesar  9 , Marek Kollar  10 , Anke von Bergwelt-Baildon  11 , Ulf Schönermarck  11 , Eveline Y Wu  12 , Lauren Blazek  13 , Vimal K Derebail  13 , Mariam Al-Attar  14 , Nina Brown  14   1 , Beatriz Sánchez Álamo  15 , Wing-Yin Leung  16 , Bryan Chang  17 , Maria Letizia Urban  18 , Federico Alberici  19 , Luis F Quintana  20 , Oliver Flossmann  21 , Silke R Brix  16   22 , Duvuru Geetha  23 , Stephen McAdoo  5 , Ajay P Dhaygude  1   2 , Andreas Kronbichler  24 , Matija Crnogorac  4
Affiliations

Clinical Presentation and Outcomes of Antineutrophil Cytoplasmic Autoantibody-Negative Pauci-Immune Glomerulonephritis

Lauren Floyd et al. Kidney Int Rep. .

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.

Keywords: ANCA-associated vasculitis; ANCA-negative; end-stage kidney disease; kidney biopsy; pauci-immune glomerulonephritis; vasculitis.

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Figures

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Graphical abstract
Figure 1
Figure 1
(a) Kaplan-Meier curve demonstrating the overall survival probability of patients with pauci-immune glomerulonephritis stratified by ANCA status up to 1 year from diagnosis. (b) Kaplan-Meier curve demonstrating the overall survival probability of patients with pauci-immune glomerulonephritis stratified by ANCA status up to 3 years from diagnosis.
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Comment in

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