title: Metabolomic Profiling in Individuals with a Failing Kidney Allograft.
abstract: BACKGROUND
  Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease.
  
  
  METHODS
  To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls.
  
  
  RESULTS
  LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels.
  
  
  CONCLUSIONS
  We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function.
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.|Transplant Medicine, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bassi
authors.affiliation: Section on Genetics and Epidemiology, Joslin Diabetes Center, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Monika A
authors.initials: MA
authors.lastname: Niewczas
authors.affiliation: San Giovanni Battista Hospital and University of Turin, Division of Nephrology, Dialysis, and Transplantation, Turin, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Biancone
authors.affiliation: San Giovanni Battista Hospital and University of Turin, Division of Nephrology, Dialysis, and Transplantation, Turin, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bussolino
authors.affiliation: Biomedical Engineering, University of Texas, Austin, TX, United States of America.
authors.forename: Sai
authors.initials: S
authors.lastname: Merugumala
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Sara
authors.initials: S
authors.lastname: Tezza
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.|Transplant Medicine, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: D'Addio
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Moufida
authors.initials: M
authors.lastname: Ben Nasr
authors.affiliation: Transplant Medicine, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valderrama-Vasquez
authors.affiliation: Transplant Medicine, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Vera
authors.initials: V
authors.lastname: Usuelli
authors.affiliation: Universita' Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: De Zan
authors.affiliation: Medicine, Al-Azhar University, Cairo, Egypt.
authors.forename: Basset
authors.initials: B
authors.lastname: El Essawy
authors.affiliation: Radiology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Venturini
authors.affiliation: Transplant Medicine, IRCCS Ospedale San Raffaele, Milan, Italy.|Universita' Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Secchi
authors.affiliation: Universita' Vita-Salute San Raffaele, Milan, Italy.|Radiology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Cobelli
authors.affiliation: Center for Clinical Spectroscopy, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lin
authors.affiliation: Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Anil
authors.initials: A
authors.lastname: Chandraker
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.|Transplant Medicine, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fiorina
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid; D003404:Creatinine / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D053719:Tandem Mass Spectrometry
chemical_list: D003404:Creatinine