title: 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 (1)H-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 (1)H 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.
authors.affiliation: Department of Critical Care, Clinical University Hospital of Valencia, Valencia, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Garcia-Simon
authors.affiliation: Central Unit of Research in Medicine, University of Valencia, Valencia, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Morales
authors.affiliation: Department of Paediatric Critical Care, University and Polytechnic Hospital La Fe, Valencia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Modesto-Alapont
authors.affiliation: Clinical Hospital Research Foundation-INCLIVA, Valencia, Spain.
authors.forename: Vannina
authors.initials: V
authors.lastname: Gonzalez-Marrachelli
authors.affiliation: Department of Critical Care, Clinical University Hospital of Valencia, Valencia, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Vento-Rehues
authors.affiliation: Department of Critical Care, Clinical University Hospital of Valencia, Valencia, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Jorda-Miñana
authors.affiliation: Department of Critical Care, Clinical University Hospital of Valencia, Valencia, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Blanquer-Olivas
authors.affiliation: Clinical Hospital Research Foundation-INCLIVA, Valencia, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Monleon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D016002:Discriminant Analysis; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D016018:Least-Squares Analysis; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D018805:Sepsis / Q000175:diagnosis* / Q000378:metabolism / Q000652:urine*; D012772:Shock, Septic / Q000175:diagnosis* / Q000378:metabolism / Q000652:urine*; D016482:Urinalysis / Q000379:methods; D055815:Young Adult
chemical_list: D015415:Biomarkers