Diagnostic and prognostic performance of urine ubiquitin carboxy-terminal hydrolase L1 across multiple acute brain injury types – A longitudinal prospective cohort study
Santtu Hellström , Antti Sajanti , Aditya Jhaveri , Abhinav Srinath , Carolyn Bennett , Ying Cao , Fredrika Koskimäki , Johannes Falter , Janek Frantzén , Seán B. Lyne , Tomi Rantamäki , Riikka Takala , Jussi P. Posti , Susanna Roine , Sulo Kolehmainen , Miro Jänkälä , Jukka Puolitaival , Romuald Girard , Melissa Rahi , Jaakko Rinne , Janne Koskimäki
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Abstract
Introduction
Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is recognized as a diagnostic and prognostic blood biomarker for traumatic brain injury (TBI). This study aimed to evaluate whether UCH-L1 concentrations measured in patients' urine post-injury could serve as a diagnostic or prognostic biomarker for outcomes in various types of acute brain injuries (ABI).
Material and methods
This pilot study included 46 ABI patients: aneurysmal subarachnoid hemorrhage (n = 22), ischemic stroke (n = 16), and traumatic brain injury (n = 8), along with three healthy controls. Urine samples were collected at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) periods post-admission. UCH-L1 and creatinine levels were quantified using ELISA. UCH-L1 concentrations were compared to functional outcomes (modified Rankin Scale, mRS) and dichotomized into favorable (mRS 0–3) and unfavorable (mRS 4–6) groups. Non-parametric statistical tests and ROC analysis was performed.
Results
UCH-L1 concentrations in healthy controls were significantly lower compared to both early and late samples after ABI (p ≤ 0.001). The diagnostic performance of urine UCH-L1 at early timepoint showed excellent discriminatory ability, with AUC of 97.6% (95% CI: 93.0–100, p = 0.006 (sensitivity 98%, specificity 100%). Urine UCH-L1 concentrations, both with and without creatinine normalization, did not distinguish between favorable and unfavorable outcomes in either early (p = 0.88 and p = 0.36) or late samples (p = 0.98 and p = 0.30) in any types of ABI.
Discussion and conclusions
Although UCH-L1 concentrations in urine did not differentiate between favorable and unfavorable outcomes, a significant difference was observed between healthy subjects and ABI patients. This finding underscores the significant diagnostic utility of urine UCH-L1 concentrations, regardless of the type of acute brain injury.
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