title: Cross-sectional examination of metabolites and metabolic phenotypes in uremia.
abstract: BACKGROUND
  Although metabolomic approaches have begun to document numerous changes that arise in end stage renal disease (ESRD), how these alterations relate to established metabolic phenotypes in uremia is unknown.
  
  
  METHODS
  In 200 incident hemodialysis patients we used partial least squares discriminant analysis to identify which among 166 metabolites could best discriminate individuals with or without diabetes, and across tertiles of body mass index, serum albumin, total cholesterol, and systolic blood pressure.
  
  
  RESULTS
  Our data do not recapitulate metabolomic signatures of diabetes and obesity identified among individuals with normal renal function (e.g. elevations in branched chain and aromatic amino acids) and highlight several potential markers of diabetes status specific to ESRD, including xanthosine-5-phosphate and vanillylmandelic acid. Further, our data identify significant associations between elevated tryptophan and long-chain acylcarnitine levels and both decreased total cholesterol and systolic blood pressure in ESRD. Higher tryptophan levels were also associated with higher serum albumin levels, but this may reflect tryptophan's significant albumin binding. Finally, an examination of the uremic retention solutes captured by our platform in relation to 24 clinical phenotypes provides a framework for investigating mechanisms of uremic toxicity.
  
  
  CONCLUSIONS
  In sum, these studies leveraging metabolomic and metabolic phenotype data acquired in a well-characterized ESRD cohort demonstrate striking differences from metabolomics studies in the general population, and may provide clues to novel functional pathways in the ESRD population.
authors.affiliation: Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. skalim@mgh.harvard.edu.
authors.forename: Sahir
authors.initials: S
authors.lastname: Kalim
authors.affiliation: Broad Institute, Cambridge, MA, USA. clary@broadinstitute.org.
authors.forename: Clary B
authors.initials: CB
authors.lastname: Clish
authors.affiliation: Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. joseph.deferio@downstate.edu.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Deferio
authors.affiliation: Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. gortiz@partners.org.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ortiz
authors.affiliation: Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. amoffet2@illinois.edu.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Moffet
authors.affiliation: Broad Institute, Cambridge, MA, USA. rgerszten@partners.org.|Cardiology Division, MGH, Boston, MA, USA. rgerszten@partners.org.|Cardiovascular Research Center, MGH, Boston, MA, USA. rgerszten@partners.org.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gerszten
authors.affiliation: Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. rthadhani@partners.org.
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.affiliation: Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. eprhee@partners.org.|Broad Institute, Cambridge, MA, USA. eprhee@partners.org.
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Rhee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D015992:Body Mass Index; D002784:Cholesterol / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000378:metabolism*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D011446:Prospective Studies; D006435:Renal Dialysis; D012709:Serum Albumin / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism*
chemical_list: D012709:Serum Albumin; D002784:Cholesterol