Kynurenic acid and kynurenine aminotransferase are potential biomarkers of early neurological improvement after thrombolytic therapy: A pilot study.

Abstract

BACKGROUND:

Biomarkers for predicting treatment response to thrombolysis in acute ischemic stroke are currently lacking. Both, animal models and clinical studies have provided evidence that the kynurenine (KYN) pathway is activated in ischemic stroke.

OBJECTIVES:

In our pilot study, we aimed to investigate whether KYN pathway enzymes and metabolites could serve as potential biomarkers for treatment response in the hyperacute phase of ischemic stroke.

MATERIAL AND METHODS:

We included 48 acute ischemic stroke patients who received thrombolysis. Blood samples were taken both before and 12 h after treatment. Concentrations of 11 KYN metabolites were determined using ultra-high-performance liquid chromatography-mass spectrometry. To assess the treatment response, we used early neurological improvement (ENI), calculated as the difference between the admission and discharge National Institutes of Health Stroke Scale (NIHSS) scores. We performed receiver operating characteristic (ROC) analysis for KYN pathway metabolites and enzymes that showed a correlation with ENI.

RESULTS:

In the samples taken before thrombolysis, significantly lower concentrations of kynurenic acid (KYNA) and kynurenine aminotransferase (KAT) activity were found in patients who had ENI (p = 0.01 and p = 0.002, respectively). According to the ROC analysis, the optimal cut-off value to predict ENI for KYNA was 37.80 nM (sensitivity (SN) 69.2%, specificity (SP) 68.4%) and 0.0127 for KAT activity (SN 92.3%, SP 73.7%).

CONCLUSIONS:

Our research is the first clinical pilot study to analyze changes in the KYN pathway in ischemic stroke patients who received thrombolytic treatment. Based on our results, baseline KYNA concentration and KAT activity could serve as potential biomarkers to predict early treatment response to thrombolysis.

• Authors: Ádám Annus, Ferenc Tömösi, Ferenc Rárosi, Evelin Fehér, Tamás Janáky, Gábor Kecskeméti, József Toldi, Péter Klivényi, László Sztriha, László Vécsei
• Journal: Advances in clinical and experimental medicine : official organ Wroclaw Medical University (Adv Clin Exp Med) Vol. 30 Issue 12 Pg. 1225-1232 (Dec 2021) ISSN: 1899-5276 [Print] Poland
• PMID: 34637198 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Transaminases
• kynurenine-oxoglutarate transaminase
• Kynurenic Acid

Topics

• Biomarkers (blood)
• Brain Ischemia (drug therapy)
• Humans
• Kynurenic Acid (blood)
• Pilot Projects
• Stroke (drug therapy)
• Thrombolytic Therapy
• Transaminases (blood)
• United States