#5627 SYSTEMATIC HISTOLOGICAL SCORING OF TUBULOINTERSTITIAL LESIONS CORRELATE WITH CLINICAL PARAMETERS IN ANCA-ASSOCIATED GLOMERULONEPHRITIS

Background and Aims Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems, including the kidney. Small vessels in the kidney include small-sized arteries (interlobular artery, afferent and efferent arteriole), capillaries (glomerular and peritubular capillary) and venules. Although crescentic ANCA glomerulonephritis (GN) is a common histological finding reflecting glomerular small vessel vasculitis, it is reasonable that manifestation of AAV could also contribute to interstitial small vessel vasculitis. Therefore, we here aimed to expand our current knowledge focusing on interstitial vasculitis in ANCA GN by systematic histological scoring of vascular lesions analogous to Banff. Method A total number of 49 kidney biopsies with confirmed renal involvement of AAV at the University Medical Center Göttingen were retrospectively included between 2015 till 2020. A renal pathologist evaluated all biopsies and was blinded to clinical data collection and analysis. A detailed methological section is provided in the Supplementary material and methods section. Results Since previous studies established that crescentic ANCA GN associates with severe kidney injury and acute deterioration of kidney function in AAV, we first systematically scored interstitial vasculitis in association with requirement of renal replacement therapy (RRT). Among all active and chronic tubulointerstitial lesions analogous to the Banff scoring system, the only association between severe kidney injury requiring RRT was observed for interstitial vasculitis in AAV reflected by peritubular capillaritis (ptc, p = 0.0002) and arteritis (v, p = 0.0069), affecting 5/49 (10.2%) and 11/49 (22.4%) of renal biopsies, respectively. Since it is known that severe deterioration of kidney function also correlates with crescentic ANCA GN, we next directly compared glomerular and tubulointerstitial lesions. The fraction of normal glomeruli was inversely associated with interstitial fibrosis (ci), total (ti) and inflammation in IFTA (i-IFTA), whereas glomerular crescents were associated with interstitial inflammation (i), tubulitis (t) and total inflammation (ti). In contrast, global glomerular sclerosis associated with less interstitial inflammation (i) but correlated with interstitial fibrosis (ci) and tubular atrophy (ct), confirming established mechansim that chronic glomerular injury leads to tubular atrophy and interstitial fibrosis. Interestingly, no association between interstitial vasculitis (ptc and v correlating with severe kidney injury) and any glomerular lesion in ANCA GN (also correlating with severe kidney injury) was observed, thereby confirming that interstitial vasculitis contributes to severe kidney injury independent of ANCA GN. By contrast, short-term renal recovery from RRT was equal in both groups, suggesting a distinct association with acute decline of kidney function at disease onset. Conclusion Taken together, by using the Banff scoring system we here expand our current knowledge of renal interstitial lesions in AAV revealing peritubular capillaritis and arteritis as important histological alterations associated with severe kidney injury in a considerable subset of AAV. Furthermore, our findings that interstitial vasculitis did not correlate with crescentic ANCA GN implicate that the characteristics of each vasculitis manifestation are independent and could further improve our understanding of mechanisms contributing to renal injury. These observations suggest that interstitial vasculitis in AAV may also affect long-term prognosis requiring further investigation.