Urinary metabonomics study on biochemical changes in an experimental model of chronic renal failure by adenine based on UPLC Q-TOF/MS

Background: Chronic renal failure (CRF) is a serious clinical symptom, occurring as the end result of all kinds of chronic kidney disease and its pathophysiological mechanism is not yet well understood. We investigated the metabolic profiling of urine samples from CRF model rats to find potential disease biomarkers and research pathology of CRF. Methods: An animal model of CRF was produced by adenine. Metabolic profiling of the urine was performed by using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS). Acquired data were subjected to principal component analysis (PCA) for differentiating the CRF and the normal control groups. Potential biomarkers were screened by using S-plot and were identified by the accurate mass, isotopic pattern and MSE fragments information obtained from UPLC Q-TOF/MS analysis. Results: 12 metabolites in urine were identified as potential biomarkers. Adenine-induced CRF rats were characterized by the increase of phytosphingosine, adrenosterone, tryptophan, 2,8-dihydroxyadenine, creatinine, and dihydrosphingosine together with the decrease of N-acetylleucine, 3-O-methyldopa, ethyl-N2-acetyl-L-argininate, dopamine, phenylalanine and kynurenic acid in urine. The altered metabolites demonstrated perturbations of amino acids metabolism, phospholipids metabolism and creatinine metabolism in CRF rats. Conclusion: This work shows that metabonomics method is a valuable tool in CRF mechanism study and assists in clinical diagnosis of CRF. (C) 2011 Elsevier B.V. All rights reserved.