Distinct Histopathological Lesions Denominate Steroid Demand During Short-Term Management of Severe ANCA-Associated Renal Vasculitides

Background: Steroid-sparing regimen are key to improved management of the potentially life-threatening autoimmune conditions ANCA-associated renal vasculitides (AArV). Though outcome guidance heavily depends on renal histopathology, impactful predictors of steroid demand remain elusive. Therefore, we aimed to identify histopathological denominators of an increased steroid demand during the initial hospitalization phase in patients with AArV. Methods: All 50 patients with biopsy-affirmed AArV were enrolled (observational period 2015-2021) in a single-center retrospective study. Medical records enabled assessment of baseline characteristics. Cumulative prednisolone demand (CPD) and intensive care unit (ICU) score APACHE II were calculated. Histopathological analysis was performed by two nephropathologists, i.a. evaluating tubulointerstitial immune cell (IC) infiltrates. Plasma cell richness vs. scarcity was assessed. ROC curve analysis, maximized Youden index calculation, survival curve analyses (Kaplan-Meier method/ log rank testing) were performed. Achieving a CPD level above the total cohort median of 2395 mg defined an event. Results: An identified cut-off of 15.5 points in APACHE II (AUC: 0.8, CI: 0.7-0.9, p=0.0003) enabled subgrouping (ICU vs. non-ICU). An increase of CPD levels (4.5g ± 1.1g vs. 2.1g ± 1.4g, p<0.0001) and a sig. elevation of serum creatinine levels (5.6 [4.4-7.2] mg/dL vs. 2.0 [1.1-3.6] mg/dL) characterized the ICU subgroup, where CPD levels independently correlated with serum creatinine elevation (β=0.65, p<0.029) and PC infiltration (β=0.71, p=0.033), being not observable in the non-ICU group. PC infiltration of >0.3% sig. predicted increased CPD levels (logrank: p=0.0036, HR 2.8, 95% CI 1.1-6.7). Conclusion: We here show that distinct histopathological lesions and critical illness have an impact on cumulative steroid demand during short-term management of severe ANCA-associated renal vasculitides, which might be implemented in future models enabling personalized outcome prediction.