Roberto Bassi 1 , 2 , Monika A. Niewczas 3 , Luigi Biancone 4 , Stefania Bussolino 4 , Sai Merugumala 5 , Sara Tezza 1 , Francesca D’Addio 1 , 2 , Moufida Ben Nasr 1 , Alessandro Valderrama-Vasquez 2 , Vera Usuelli 2 , Valentina De Zan 6 , Basset El Essawy 7 , Massimo Venturini 8 , Antonio Secchi 2 , 6 , Francesco De Cobelli 6 , 8 , Alexander Lin 9 , Anil Chandraker 10 , Paolo Fiorina 1 , 2 , *
4 January 2017
Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease.
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.
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.