Systematic Scoring of Tubular Injury Patterns Reveals Interplay between Distinct Tubular and Glomerular Lesions in ANCA-Associated Glomerulonephritis

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis, most frequently presenting as microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). Acute tubular injury with the presence of tubulitis was previously reported to be of prognostic value in ANCA glomerulonephritis (GN). In particular, distinct tubular injury lesions were associated with the deterioration of kidney function at AAV disease onset, as well as renal resistance to treatment, and higher risk of progression to composite outcome in patients with AAV. To expand our knowledge regarding distinct tubular lesions in AAV, we aimed to describe acute tubular injury patterns in association with glomerular lesions in ANCA GN by systematic histological scoring. Methods: A total number of 48 renal biopsies with confirmed renal involvement of AAV admitted to the University Medical Center Gottingen from 2015 to 2020 were retrospectively examined. By systematic scoring of tubular injury lesions, the association between clinical parameters, laboratory markers, and histopathological findings was explored. Results: We have shown that cellular casts in renal biopsies were frequently observed in the majority of cases with ANCA GN. Furthermore, we showed that tubular epithelial simplification with dilatation correlated with MPA and MPO subtypes, C3c hypocomplementemia, severe renal involvement, and uACR. Red blood cell (RBC) casts were associated with increased levels of C-reactive protein (CRP), leukocyturia, and hematuria. Finally, we found that hyaline casts were associated with an increased fraction of glomeruli with global glomerular sclerosis. Conclusions: Acute tubular injury patterns were correlated with active ANCA GN, whereas tubular injury lesions reflecting the later stages of kidney disease correlated with chronic glomerular lesions. These results suggest an interplay between different renal compartments.