The low solubility of 2,8-dihydroxyadenine would lead to precipitation in renal tubules and then this led to accumulation of blood urea nitrogen and Scr. Long-term feeding adenine to rats caused metabolic abnormalities similar to CKD clinical symptoms in humans. CKD in humans can be reproduced in the rodent animal SAR131675 1433953-83-3 including rats or mice by adenine; and adenine-induced CKD model can provide a special opportunity to study the CKD development and pathogenesis as well as effects of interventions that target disease progression due to the presence of metabolic abnormalities, declining renal function and chronic progressive tubulo-interstitial nephritis. In this study, UPLC-QTOF/HDMS were applied to investigate CKD pathological changes and the therapeutic effects of ergone. Partial least squares-discriminate analysis, correlation analysis and heatmap analysis were performed for investigating the metabolic changes. This study provides new insights into the pathological changes that occur during the initiation and progression of CKD. This work may also offer an approach to evaluate therapeutic effects of anti-fibrogenic drugs and their mechanisms of action. Progressive renal diseases including human renal diseases and animal models are the consequence of a process of destructive fibrosis. Typical characteristic of interstitial fibrosis is excess deposition of extracellular matrix components, accumulated collagen proteins and associated glycoproteins. Many investigators have focused principally on the molecular pathogenesis of interstitial fibrosis owing to the correlation between the level of interstitial fibrosis and kidney functional injury. TGF-b was a central mediator of renal fibrosis and TGF-b1 has been most extensively investigated in renal fibrosis. TGF-b1 induced expression of CTGF, and CTGF can in turn enhance TGF-b1 signaling, along with a number of other pro-fibrotic factors including ED-1, vascular endothelial growth factor and insulin-like growth factor-1. bFGF stimulates release of preformed latent TGF-b1 from proximal tubular cells and bFGF expression also increases in tubular and/or interstitial cell. To study the relation between identified biomarkers and proteins, the expression of TGF-b1, ED-1, CTGF, bFGF and collagen I proteins was evaluated by Western blotting method. Upregulated expression of TGF-b1, ED-1, CTGF, bFGF and collagen I was observed in the CKD group compared with control group. However, amelioration of expression of these proteins was observed after oral administration of ergone. In the current study, it was found that polyunsaturated fatty acids were the most important CKD-related metabolites and ten polyunsaturated fatty acids accounts for 60% of all the identified metabolites. Polyunsaturated fatty acids were the major components of cytoplasmic membrane and they were related to atherosclerotic and inflammatory diseases. DHA, 5-HETE and EPA were reversed completely by treatment with ergone. Beneficial effects of n-3 polyunsaturated fatty acids including DHA and EPA were observed in animal models and human nephropathies. Levels of DHA, EPA and LA were remarkably lower in hemodialysis patients than in CKD patients.