Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. To explore metabolome abnormalities in individuals with a failing kidney allograft, we analyzed by liquid/gas cromatography-mass spectrometry (LC/GS-MS; for ex vivo profiling of serum and urine) and three dimensional nuclear magnetic resonance spectroscopy (3D NMR; 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 individuals were chosen as controls. LC/GS-MS analysis revealed a dose-response associationbetween 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, DMA, 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 3D NMR of the kidney allograft revealed significant reduction of the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels We report an association between GFR and altered metabolic profile in renal transplant individuals with different degrees of kidney graft function.

CITATION INFORMATION: Bassi R, Niewczas M, Biancone L, Bussolino S, Lin A, Chandraker A, Fiorina P. Metabolomic Profiling of Individuals with Failing Kidney Allograft. Am J Transplant. 2016;16 (suppl 3).

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