Urine metabolomics for futile recanalization in acute large vessel occlusion stroke: a pilot exploratory study

Abstract Background and objective Endovascular treatment (EVT) effectively treats acute ischemic stroke (AIS) from anterior circulation large vessel occlusion (LVO), but ~50% of successfully recanalized patients experience futile recanalization (FR). This pilot exploratory study characterized preoperative urine metabolic profiles of FR after EVT in LVO-AIS to screen candidate metabolites and pathways. Methods Patients with anterior circulation LVO-AIS who underwent successful EVT were prospectively enrolled. Preoperative urine was analyzed by untargeted LC–MS/MS. FR was defined as 90-day mRS > 2. Differential metabolites were screened using VIP > 1 and P < 0.05 (exploratory threshold, FDR uncorrected). KEGG pathway enrichment, logistic regression, and ROC curves were applied. Results Among 42 patients (21 FR, 21 non-FR), three candidate metabolites that were upregulated in FR were preliminarily identified: thiamine pyrophosphate, dehydroascorbic acid, and γ-glutamylcysteine. They were enriched in glutathione/ascorbate metabolism, ferroptosis, and glycolysis/gluconeogenesis, involving antioxidant stress, energy metabolism, and cell death. Dehydroascorbic acid and γ-glutamylcysteine were significantly associated with FR ( P < 0.05); thiamine pyrophosphate showed borderline significance ( P = 0.061). γ-Glutamylcysteine negatively correlated with ASPECTS ( r = −0.558, P < 0.001), and thiamine pyrophosphate with collateral circulation score ( r = −0.384, P = 0.012). The three-metabolite panel showed a preliminary discriminative ability with an AUC of 0.893 (95% CI 0.780–0.915). Conclusion This pilot exploratory study provides the first description of preoperative urine metabolic alterations associated with FR after EVT in LVO-AIS, suggesting redox imbalance and energy disturbance as potential mechanisms, but findings require validation in larger cohorts.