Metabolic profiling identifies the significance of caffeine metabolism in CKD

Background: To identify the most important metabolic pathways by screening metabolites that improve the progression of CKD stage through metabolic profiling and thus to identify relevant targets that may improve renal function. Methods: : Clinical data were collected in 145 chronic kidney disease (CKD) participants, and their measurements of GFR (mGFR) were measured by the iohexol method. Untargeted metabolomics analysis was performed by UPLC-MS /MSUPLC–MSMS/MS assays. Procession, extraction and peak identification of the raw mass spectrometry data were carried out, and metabolites were identified. All participants were divided into four groups according to mGFR. Metabolomic data were analyzed by MetaboAnalyst 5.0, and one-way ANOVA, PCA, and PLS-DA were carried out to identify differential metabolites for further analysis. The open database sources of MBRole2.0, including KEGG and HMDB, were used to identify significant metabolic pathways in CKD. Results: : Four metabolic pathways were classified as important in the progression of CKD, and the most significant pathway was caffeine metabolism. A total of 12 metabolites were enriched in caffeine metabolism, four of which decreased with the deterioration of CKD stage, and two of them increased with the deterioration of CKD stage. Of the four decreased metabolites, the most important was caffeine, which may improve renal function. Conclusions: : Caffeine metabolism appears to be the most important pathway in the progression of CKD. Caffeine may help to improve the progression of CKD.