Bassi, RobertoNiewczas, MonikaBiancone, LuigiBussolino, StefaniaMerugumala, SaiTezza, SaraD’Addio, FrancescaBen Nasr, MoufidaValderrama-Vasquez, AlessandroUsuelli, VeraDe Zan, ValentinaEl Essawy, BassetVenturini, MassimoSecchi, AntonioDe Cobelli, FrancescoLin, AlexanderChandraker, AnilFiorina, Paolo2017-02-182017Bassi, R., M. A. Niewczas, L. Biancone, S. Bussolino, S. Merugumala, S. Tezza, F. D’Addio, et al. 2017. “Metabolomic Profiling in Individuals with a Failing Kidney Allograft.” PLoS ONE 12 (1): e0169077. doi:10.1371/journal.pone.0169077. http://dx.doi.org/10.1371/journal.pone.0169077.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:30371180Background: 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.en-USBiology and Life SciencesAnatomyRenal SystemKidneysMedicine and Health SciencesSurgical and Invasive Medical ProceduresTransplantationOrgan TransplantationRenal TransplantationUrinary System ProceduresPhysiologyRenal PhysiologyGlomerular Filtration RateBiochemistryMetabolismMetabolitesMetabolomicsSpectrum analysis techniquesNMR spectroscopyCorrelation SpectroscopyTwo-Dimensional Correlation SpectroscopyTwo-dimensional NMR spectroscopyBody FluidsUrineJournal Article2017-02-1810.1371/journal.pone.0169077