Systematic Histological Scoring Reveals More Prominent Interstitial Inflammation in Myeloperoxidase-ANCA Compared to Proteinase 3-ANCA Glomerulonephritis

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic vasculitis, most frequently presenting as microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). Kidney involvement is a common and severe complication of ANCA AAV which is observed in a considerable subset of patients, mainly affecting glomeruli. However, tubulointerstitial lesions have also been described in ANCA glomerulonephritis (GN). Therefore, we aim to describe active and chronic tubulointerstitial lesions in ANCA GN subtypes by systematic scoring analogous to the Banff scoring system while also utilizing clinical and laboratory findings. Methods: A total of 49 kidney biopsies with ANCA GN were retrospectively included in a single-center cohort study between 2015-2020. Results: We report that MPO-ANCA GN is associated with more severe deterioration of kidney function independent of systemic markers of AAV disease activity, and is also associated with increased proteinuria in MPO-ANCA GN and a decreased fraction of normal glomeruli. Finally, MPO-ANCA GN showed distinct, active, and chronic tubulointerstitial lesions. Conclusion: New insights into the pathophysiology of both entities, as well as differences in the clinical presentation of MPO- versus PR3-ANCA GN, could potentially pave the way for more precise treatment regimens. Therefore, it is important to understand the differences in histopathological presentation, especially in yet underestimated active tubulointerstitial lesions of ANCA GN subtypes. This research could further improve our understanding of distinct pathophysiological mechanisms.