Prognosis Biomarkers of Severe Sepsis and Septic Shock by 1H NMR Urine Metabolomics in the Intensive Care Unit

Abstract

Early diagnosis and patient stratification may improve sepsis outcome by a timely start of the proper specific treatment. We aimed to identify metabolomic biomarkers of sepsis in urine by 1H-NMR spectroscopy to assess the severity and to predict outcomes. Urine samples were collected from 64 patients with severe sepsis or septic shock in the ICU for a 1H NMR spectra acquisition. A supervised analysis was performed on the processed spectra, and a predictive model for prognosis (30-days mortality/survival) of sepsis was constructed using partial least-squares discriminant analysis (PLS-DA). In addition, we compared the prediction power of metabolomics data respect the Sequential Organ Failure Assessment (SOFA) score. Supervised multivariate analysis afforded a good predictive model to distinguish the patient groups and detect specific metabolic patterns. Negative prognosis patients presented higher values of ethanol, glucose and hippurate, and on the contrary, lower levels of methionine, glutamine, arginine and phenylalanine. These metabolites could be part of a composite biopattern of the human metabolic response to sepsis shock and its mortality in ICU patients. The internal cross-validation showed robustness of the metabolic predictive model obtained and a better predictive ability in comparison with SOFA values. Our results indicate that NMR metabolic profiling might be helpful for determining the metabolomic phenotype of worst-prognosis septic patients in an early stage. A predictive model for the evolution of septic patients using these metabolites was able to classify cases with more sensitivity and specificity than the well-established organ dysfunction score SOFA.

Metabolomics as a Driver in Advancing Precision Medicine in Sepsis

“…48 Ultimately, the strength and added value of metabolomics in sepsis for both children and adults may be when it is combined with clinical data and other measurements to improve prediction of outcomes and demonstrate enhanced performance when compared with currently available diagnostic tests including procalcitonin, C-reactive protein, and lactate levels. 43,45,55 In an example of this strategy, profiling children early after presentation in the emergency department using metabolomics and inflammatory protein mediators differentiated children who did and did not require ICU care. This application of metabolomics may aid in triage decisions and risk stratification in sepsis, particularly in clinical environments without pediatric expertise.…”

Metabolic Disturbances in Adult-Onset Still’s Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis

“…LC/MS-based metabolomics approach has potential implications for disease diagnosis and prediction [18,28–30]. Our study is the first to use UPLC-QTOF/MS-based metabolomics to reveal 18 differentially expressed metabolites in AOSD patients compared with healthy subjects, and then use LC/MRM-MS analysis to validate 13 metabolites in replication cohort with a high AUC and specificity.…”

Metabolomics in Sepsis and Its Impact on Public Health

“…Both NMR and MS have been employed in the study of several metabolites in different biological fluids and tissues, mainly blood (serum and whole blood), bronchoalveolar fluid, and urine, in animal models as well as in humans [68-70]. Study design strategies involve different approaches, ranging from targeting certain pathways [71] to studying metabolite classes and mitochondrial dysfunction [72, 73].…”