Prediction of Renal Relapse in ANCA Vasculitis: The Role of Urinary T Cells and Tubular Epithelial Cells

Background: Renal relapse in ANCA-associated vasculitis (AAV) remains a major challenge, as conventional biomarkers such as ANCA titers, proteinuria, and serum creatinine lack specificity in predicting disease flares. Emerging evidence suggests that urinary CD4+ T cells may serve as a novel biomarker for detecting subclinical immune activation preceding renal relapse. This study aimed to evaluate the predictive value of urinary CD4+ T lymphocytes in AAV patients in remission. Methods: The PRE-FLARED study was a prospective, multicenter cohort study includ-ing 102 AAV patients in clinical remission. Urinary CD4+ and CD8+ T cells, their memory subsets, and tubular epithelial cells (TECs) were quantified by flow cytometry. Patients were followed for 12 months to assess renal relapse risk. The predefined pri-mary outcome was renal relapse at six months, defined according to BVAS criteria. Di-agnostic performance was evaluated using ROC curve analysis, while Kaplan-Meier survival analysis assessed relapse-free survival. Results: At six months, 10 of 102 patients (9.8%) experienced a renal relapse. Baseline urinary CD4+ T cell counts were significantly elevated in relapsing patients (median: 811 vs. 38 cells/dL, p < 0.0001). ROC analysis yielded an AUC of 0.88, outperforming ANCA titers, proteinuria, and serum creatinine. A threshold of 490 CD4+ T cells/dL pro-vided 97.8% specificity and 60% sensitivity for relapse prediction. Kaplan-Meier analysis confirmed that patients exceeding this threshold had a 29-fold higher risk of relapse. Urinary TEC counts showed no significant association with relapse. Furthermore CD4+ T cells correlated weakly with kidney function decline (ΔeGFR: ρ = -0.24, p = 0.014). Conclusion: Urinary CD4+ T cells are a robust, non-invasive biomarker for short-term relapse prediction in AAV, providing superior specificity compared to conventional markers. Their integration into routine surveillance protocols could enable earlier inter-vention and tailored immunosuppression. However, the long-term predictive value re-mains limited, warranting further research on multimodal biomarker strategies incorpo-rating urinary CD4+ T cells, sCD163, and MCP.