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Metabolomic Profiling in Individuals with a Failing Kidney Allograft

Article scientifique 2017 Anglais

Résumé

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.

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Bassi, R., Niewczas, M., Biancone, L., Bussolino, S., Merugumala, S., Tezza, S., D’Addio, F., Nasr, M., Valderrama-Vasquez, A., Usuelli, V., Zan, V., Essawy, B., Venturini, M., Secchi, A., Cobelli, F., Lin, A., Chandraker, A., Fiorina, P. (2017). Metabolomic Profiling in Individuals with a Failing Kidney Allograft. https://doi.org/10.1371/journal.pone.0169077

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