Potential urine biomarkers from a high throughput metabolomics study of severe sepsis in a large Asian cohort

Abstract

Severe sepsis (SS) is a main cause of death in hospitalized patients worldwide. There is an urgent need for accurate biomarkers for early diagnosis of SS. Metabolomics technologies allow high-throughput screening of metabolite biomarkers. Non-targeted mass spectrometry (MS) was used to characterize sensitive and economical peripheral biomarker(s) associated with the urine metabolome from SS patients. In this study, urine samples were obtained from controls and age-matched patients with SS. Metabolic differences among SS and control subjects were identified based on orthogonal signal correction-partial least squares discriminant analysis. Sphingosine, 5-methylcytidine, 3-dehydrocarnitine, 4-acetamido-2-aminobutanoic acid and phenyllactic acid in the SS subjects were significantly different from the control subjects. The receiver operating characteristic curve of the differential expression of these metabolites was also performed to demonstrate the utility of these biomarkers for diagnosis of SS. Three metabolites comprising sphingosine, 5-methylcytidine and 3-dehydrocarnitine were selected as candidate biomarkers and validation in separate and independent patient cohorts. Mass-spectrometry urine profiling proved to be an efficient and convenient tool for diagnosis and screening of SS in a high-risk population.