Tocilizumab in the Treatment of Chronic Antibody-Mediated Rejection Post Kidney Transplantation: Clinical and Histological Monitoring

Introduction: Chronic antibody-mediated rejection (cAMR) has very few effective therapeutic options. Interleukin-6 is an attractive target because it is involved in inflammation and humoral immunity. Therefore, the use of tocilizumab (anti-IL6 receptor, TCZ) is a potential valuable therapeutic option to treat cABMR in kidney-transplant (KT) recipients.Materials and Methods: This single-center retrospective study included all KT recipients that received monthly TCZ infusions in the setting of cABMR, between August 2018 and July 2021. We assessed 12-month renal function and KT histology during follow-up.Results: Forty patients were included. At 12-months, eGFR was not significantly different, 41.6 ± 17 vs. 43 ± 17 mL/min/1.73 m2 (p = 0.102) in patients with functional graft. Six patients (15%) lost their graft: their condition was clinically more severe at the time of first TCZ infusion. Histological follow-up showed no statistical difference in the scores of glomerulitis, peritubular capillaritis, and interstitial fibrosis/tubular atrophy (IFTA). Chronic glomerulopathy score however, increased significantly over time; conversely arteritis and inflammation in IFTA ares improved in follow-up biopsies.Conclusion: In our study, the addition of TCZ prevented clinical and histological worsening of cABMR in KT recipients, except for more severely ill patients. Randomized studies are needed to clarify the risk/benefit of TCZ in cABMR.

POS0247 INTERSTITIAL ANCA-ASSOCIATED VASCULITIS ASSOCIATES WITH SEVERE KIDNEY INJURY INDEPENDENT OF GLOMERULONEPHRITIS

Background: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.Objectives: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.Methods: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 (SH) 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.Disclosure of Interests:None declared