Outcomes and Validation of Histopathological Scores in Pediatric ANCA-vasculitis

Introduction: Although anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is rare in children, kidney involvement is both common and potentially severe. Data on the clinico-pathological presentation and progression of kidney involvement in pediatric AAV are limited. Methods: This multicentric, retrospective, observational study aims to characterize kidney involvement in pediatric AAV, through a centralized pathology review of kidney biopsies and comparisons with an adult AAV cohort. Results: Eighty-one pediatric patients (median age 12.7 years, 23% male) were included over 20 years. Compared with adults (median age 66 years, 52% male), children presented with more frequent nephrotic-range proteinuria (42% vs. 18%, P < 0.001), lower hemoglobin levels (8.7 vs. 9.7 g/dl, P < 0.001), and more common cutaneous (24% vs. 9%, P = 0.001) and gastrointestinal involvement (18% vs. 3%, P < 0.001); histologically, more crescentic (P < 0.001) and fewer focal forms (P < 0.001), less interstitial fibrosis and tubular atrophy (IF/TA 0: 41% vs. 19%, P = 0.001) and more interstitial inflammation (ti1-2-3 per Banff classification: 66% vs. 47%, P = 0.025). For induction treatment children had a more frequent use of rituximab (65% vs. 43%, P = 0.001) and plasma exchange (31% vs. 15%, P = 0.004). Kidney outcomes were comparable to adults. The Berden classification, ANCA Renal Risk Score (ARRS), and ANCA Kidney Risk Score (AKRiS) showed good predictive accuracy for pediatric patients. Repeat biopsies demonstrated reduced activity and progression towards fibrosis. Conclusion: Pediatric patients present a more active kidney histology than adults, a more frequent nephrotic-range proteinuria and more severe anemia at presentation. Despite this, outcomes are comparable to adults. Berden, ARRS, and AKRiS can be used for predicting kidney prognosis in the pediatric population.