High-resolution mass spectrometry for exploring metabolic signatures of sepsis-induced acute kidney injury

Abstract

Sepsis is a commonly encountered scenario in an intensive care unit (ICU), and the kidney is one of the organs frequently affected. Sepsis-induced acute kidney injury (SIAKI) contributes to the high mortality and morbidity. A major reason for this is the lack of biomarkers for SIAKI in ICU patients. Metabolic phenotype signatures of SIAKI may enable metabolite biomarker discovery for diagnosis. With the progress of the Omics, currently, high-resolution mass spectrometry-based metabolomics is being used for biomarker discovery. Orthogonal partial least-squares discriminant analysis (OPLS-DA) afforded a good predictive tool to distinguish patients and detect the specific metabolic patterns. Variable importance for projection (VIP) was conducted to identify potential biomarkers for SIALI. Receiver operating characteristic analysis was performed for evaluating the diagnostic accuracy of potential metabolites. In this study, some potential biomarkers were successfully discovered by the commonly used variable selection method, VIP of OPLS-DA. Six metabolites were identified as the potential biomarkers for distinguishing SIAKI patients. Meanwhile, malonylcarnitine, D-glutamine and 3-methoxytyrosine were found to be the important variables to distinguish between SIAKI patients and healthy cases. According to the receiver operating characteristic analysis, we reported malonylcarnitine, with an area under concentration–time curve value of 0.995, maybe as a novel diagnostic biomarker associated with SIALI patients. Our results indicate that serum metabolic profiling by high-resolution mass spectrometry might be a helpful tool for determining the metabolic phenotype of SIAKI patients.