LAUSR

Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We have previously reported that severe deterioration of kidney function is associated with necrotizing and crescentic ANCA glomerulonephritis (GN), classified into Berden’s crescentic class or ANCA renal risk score (ARRS) high risk. However, tubulointerstitial inflammation associated with either histopathological subgrouping or ARRS remains elusive. Furthermore, clinical and laboratory markers of AAV disease severity or deterioration of kidney function in association with inflammatory findings in the kidney have not been described yet. Since aggressive immunosuppressive therapy is recommended for remission induction especially in severe cases of AAV, we here aimed to expand our current knowledge with regard to histopathological classification of tubulointerstitial injury and inflammatory findings analogous to the Banff classification. A total number of 50 renal biopsies with confirmed renal involvement of AAV were retrospectively included between 2015 till 2020 in a single-center observational study. Renal biopsies were evaluated for either focal, crescentic, mixed or sclerotic class (according to Berden et al.) and ARRS low, intermediate or high risk (according to Brix et al.). Inflammatory and fibrotic tubulointerstital alterations were evaluated analogous to Banff scoring system for allograft pathology. We here show that distinct inflammatory lesions are associated with glomerular findings classified into either histopathological subgrouping or ARRS. Furthermore, interstitial inflammation and tubulitis correlate with disease severity and decline of kidney function in AAV. Finally, we provide data that tubulointerstitial injury and inflammatory findings correlate with short-term outcome in response to aggressive immunosuppression and remission induction therapy. In summary, we here provide evidence that a systematic scoring of inflammatory and degenerative tubulointerstitial lesions correlate with severe renal impairment and short-term response to remission induction therapy. Since aggressive immunosuppressive therapy is recommended for remission induction especially in severe cases of AAV, systematic histopathological scoring of tubuloinsterstital lesions could further improve our current knowledge of ANCA GN progression.