Cluster Analysis of a Monocentric Cohort of ANCA-Associated Vasculitis: Implications on Induction-Maintenance Therapeutic Strategies and Role of Repeat Kidney Biopsy

Background: ANCA-associated vasculitis (AAVs) are potentially organ or life-threatening. While quite a consensus on induction therapy has been achieved, about maintenance therapy (MT) is still to be investigated. This retrospective study analyzes the clinical and histological characteristic of patients (pts) who underwent a diagnosis of AAVs at our Center between January 2014 and May 2024 and look for markers that can identify clusters of patients most at risk of an unfavorable outcome. Methods: All the pts with AAV with biopsy proven renal involvement evaluated at our Center from January 1, 2014 to May 31, 2024 were included in this retrospective study. Results: Seventy-one pts with AAVs with biopsy-proven renal involvement were included. Seventeen pts had a renal limited vasculitis, 54 systemic involvement. Mean serum creatinine (sCr) at diagnosis was 2.65 mg/dL, with a mean eGFR of 29 ml/min. 19 pts were dialysis (HD) dependent. About 60% of the free-HD pts had an eGFR <30 ml/min. Twenty-five pts received an induction with Rituximab (RTX), 8 cyclophosphamide (CYC) and 38 RTX associated with CYC. After remission, 33 (46.5%) patients had a complete renal response (RR), 27 (38%) partial RR, and 11 (15.5%) remained HD dependent. 50 (70%) pts did not receive any MT. At the end of the follow up (mean 49 months), 55 (77.5%) pts stayed on sustained clinical remission, while 16 (22.5%) had a relapse after a mean time of 29 months. 25 out of 71 pts (35%) underwent a repeated renal biopsy, that guided a change in ongoing therapy in 20 cases. The subsequent cluster analysis identified 3 clusters at higher risk of poor outcomes, characterized by crescentic forms, severe renal impairment, low sC3 and high IgG serum levels. Conclusion: Data from the present cohort of patients followed-up over the last 10 years confirmed the effectiveness of a personalized treatment and allowed the elaboration of an algorithm showing how, once a clinical remission is achieved, the AAV patient is managed according to our school strategy. Our ultimate target is tailoring treatment strategies that not only adapt to changing clinical conditions. This approach promises a more nuanced and effective management of AAV, potentially reducing unnecessary exposure to long-term immunosuppression while maintaining disease control.