Urinary CD4⁺ T Cells Predict Renal Relapse in ANCA-Associated Vasculitis

Background: In ANCA-associated vasculitis (AAV) there is a lack of biomarkers for predicting renal relapse. Urinary T cells have been shown to differentiate active glomerulonephritis from remission in AAV, but their predictive value for renal flares remains unknown. Methods: The PRE-FLARED study is a prospective multicenter biomarker study including 102 individuals with AAV in remission, aimed to predict renal relapse by quantifying urinary CD4+ T cell subsets using flow cytometry at baseline and monitoring clinical outcomes over a six-month follow-up. Results: Among the participants, ten experienced renal relapses, two had non-renal flares, and 90 remained in stable remission. The median baseline urinary CD4+ T cell count was significantly higher in patients who relapsed compared to those in remission. Receiver operator characteristic (ROC) curve analysis of urinary CD4+ T cell counts showed an area under the curve (AUC) value of 0.88 for predicting renal flares, outperforming ANCA titers, hematuria, and proteinuria. Using a cut-off of 490 CD4+ T cells per 100 mL urine, the sensitivity and specificity in identifying patients with future renal flares were 60% and 97.8%, respectively. In a post-hoc analysis, combining urinary CD4+ T cell counts with PR3-ANCA levels suggested improved predictive performance in the PR3+ subgroup. Additionally, the number of urinary CD4+ T cells showed a limited correlation with a decline in glomerular filtration rate (GFR) and an increase in proteinuria over the follow-up period. Conclusions: The study concluded that urinary CD4+ T cell counts could identify AAV patients at a substantial risk of renal relapse within six months. Combining these counts with ANCA levels further improved the prediction of relapse. These findings have implications for personalized management strategies in patients with renal AAV.