Risk stratification for renal outcomes in ANCA-associated vasculitides using established scores and histopathological criteria

Abstract Background Glomerulonephritis is a common, organ-threatening manifestation in ANCA-associated vasculitis (AAV). Various clinico-histological scores have been developed assessing the risk of kidney failure, including the simplified ANCA kidney risk score (AKRiS). Methods This retrospective study included 220 patients with biopsy-confirmed kidney involvement of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) recruited from four tertiary European referral centers. We collected biometric and clinical baseline data, disease activity parameters, AKRiS classes and histomorphological features. We examined the occurrence of a composite endpoint (ie all-cause mortality or kidney failure defined as persistent estimated glomerular filtration rate eGFR decline 15 mL/min/1.73 m² or kidney replacement therapy after ≥6 months, respectively) within individual AKRiS and precursor risk classes. Results GPA and MPA patients exhibited largely comparable baseline characteristics and treatment regimens. Histological analysis revealed that MPA biopsies showed significantly more sclerosis, interstitial fibrosis and tubular atrophy (IFTA) than their GPA counterparts. Histologically, most patients fell into focal and mixed classes, which mainly transitioned into low- and medium-risk AKRiS categories. Higher risk classifications predominantly derived from crescentic and sclerotic classes. Patients categorized as medium risk in the precursor score most frequently transitioned to lower AKRiS scores. AKRiS stratification was superior to the ANCA Renal Risk Score (ARRS) in the prediction of adverse outcomes over the entire period (AUC 0.76, C-Index 0.899). Conclusions The AKRiS score was found to be effective in predicting kidney failure and a strong composite kidney endpoint in a large European AAV cohort, despite slight differences in histological and event patterns between GPA and MPA under comparable treatment regimens.