title: Metabolites Associated With Malnutrition in the Intensive Care Unit Are Also Associated With 28-Day Mortality.
abstract: We hypothesized that metabolic profiles would differ in critically ill patients with malnutrition relative to those without.
  
  
  
  We performed a prospective cohort study on 85 adult patients with systemic inflammatory response syndrome or sepsis admitted to a 20-bed medical intensive care unit (ICU) in Boston. We generated metabolomic profiles using gas and liquid chromatography and mass spectroscopy. We followed this by logistic regression and partial least squares discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis and network model construction of chemical-protein target interactions to identify groups of metabolites and pathways that were differentiates in patients with and without malnutrition.
  
  
  
  Of the cohort, 38% were malnourished at admission to the ICU. Metabolomic profiles differed in critically ill patients with malnutrition relative to those without. Ten metabolites were significantly associated with malnutrition ( P < .05). A parsimonious model of 5 metabolites effectively differentiated patients with malnutrition (AUC = 0.76), including pyroglutamine and hypoxanthine. Using pathway enrichment analysis, we identified a critical role of glutathione and purine metabolism in predicting nutrition. Nutrition status was associated with 28-day mortality, even after adjustment for known phenotypic variables associated with ICU mortality. Importantly, 7 metabolites associated with nutrition status were also associated with 28-day mortality.
  
  
  
  Malnutrition is associated with differential metabolic profiles early in critical illness. Common to all of our metabolome analyses, glutathione and purine metabolism, which play principal roles in cellular redox regulation and accelerated tissue adenosine triphosphate degradation, respectively, were significantly altered with malnutrition.
authors.affiliation: 1 Department of Nutrition, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Kris M
authors.initials: KM
authors.lastname: Mogensen
authors.affiliation: 2 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lasky-Su
authors.affiliation: 3 Pulmonary & Critical Care Medicine, Stanford University Medical Center, Palo Alto, California, USA.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Rogers
authors.affiliation: 4 Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Baron
authors.affiliation: 4 Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Fredenburgh
authors.affiliation: 5 Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: James
authors.initials: J
authors.lastname: Rawn
authors.affiliation: 5 Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Robinson
authors.affiliation: 4 Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Massarro
authors.affiliation: 6 Department of Medicine, New York-Presbyterian Hospital, New York, New York, USA.
authors.forename: Augustine M K
authors.initials: AM
authors.lastname: Choi
authors.affiliation: 7 The Nathan E. Hellman Memorial Laboratory, Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Christopher
mesh_terms: D000328:Adult; D000368:Aged; D001900:Boston; D015331:Cohort Studies; D016638:Critical Illness / Q000401:mortality*; D005260:Female; D005971:Glutamates / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019271:Hypoxanthine / Q000378:metabolism; D007362:Intensive Care Units; D008297:Male; D044342:Malnutrition / Q000378:metabolism*; D055442:Metabolome; D008875:Middle Aged; D009752:Nutritional Status; D011446:Prospective Studies; D011687:Purines / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives
chemical_list: D005971:Glutamates; D011687:Purines; D019271:Hypoxanthine; C017697:pyroglutamine-4-nitroanilide; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; C030985:purine
keywords: critical care; intensive care; metabolism; metabolomics; mortality; nutrition status