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.
Metabolomic profiling in individuals with a failing kidney allograft / R. Bassi, M.A. Niewczas, L. Biancone, S. Bussolino, S. Merugumala, S. Tezza, F. D'Addio, M.B. Nasr, A. Valderrama Vasquez, V. Usuelli, V. De Zan, B. El Essawy, M. Venturini, A. Secchi, F. De Cobelli, A. Lin, A. Chandraker, P. Fiorina, M. Ben Nasr. - In: PLOS ONE. - ISSN 1932-6203. - 12:1(2017 Jan), pp. 0169077.1-0169077.14.
|Titolo:||Metabolomic profiling in individuals with a failing kidney allograft|
FIORINA, PAOLO (Ultimo) (Corresponding)
|Parole Chiave:||Medicine (all); Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
|Data di pubblicazione:||gen-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0169077|
|Appare nelle tipologie:||01 - Articolo su periodico|