Metabolic profiling identifies the significance of caffeine metabolism in CKD

Xinghua Guo; Hongquan Peng; Peijia Liu; Leile Tang; Jia Fang; Chiwa Aoieong; Tou Tou; Tsungyang Tsai; Xun Liu

doi:10.3389/fbioe.2023.1006246

Metabolic profiling identifies the significance of caffeine metabolism in CKD

Front Bioeng Biotechnol. 2023 Feb 17:11:1006246. doi: 10.3389/fbioe.2023.1006246. eCollection 2023.

Authors

Xinghua Guo¹, Hongquan Peng², Peijia Liu³, Leile Tang⁴, Jia Fang¹, Chiwa Aoieong², Tou Tou², Tsungyang Tsai², Xun Liu⁵

Affiliations

¹ Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
² Department of Nephrology, Kiang Wu Hospital, Macau, Macao SAR, China.
³ Department of Nephrology, GuangZhou Eighth People's Hospital, GuangZhou Medical University, Guangzhou, Guangdong, China.
⁴ Department of Cardiovasology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
⁵ Department of Nephrology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.

Abstract

Background: With the development of chronic kidney disease (CKD), there are various changes in metabolites. However, the effect of these metabolites on the etiology, progression and prognosis of CKD remains unclear. Objective: We aimed to identify significant metabolic pathways in CKD progression by screening metabolites through metabolic profiling, thus identifying potential targets for CKD treatment. Methods: Clinical data were collected from 145 CKD participants. GFR (mGFR) was measured by the iohexol method and participants were divided into four groups according to their mGFR. Untargeted metabolomics analysis was performed via UPLC-MS/MSUPLC-MSMS/MS assays. Metabolomic data were analyzed by MetaboAnalyst 5.0, one-way ANOVA, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) 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 progression. Results: Four metabolic pathways were classified as important in CKD progression, among which the most significant was caffeine metabolism. A total of 12 differential metabolites were enriched in caffeine metabolism, four of which decreased with the deterioration of the CKD stage, and two of which increased with the deterioration of the CKD stage. Of the four decreased metabolites, the most important was caffeine. Conclusion: Caffeine metabolism appears to be the most important pathway in the progression of CKD as identified by metabolic profiling. Caffeine is the most important metabolite that decreases with the deterioration of the CKD stage.

Keywords: caffeine; caffeine metabolism; chronic kidney disease; glomerular filtration rate; metabolomics.

Grants and funding

This study was supported by the Science and Technology Development Fund, Macau SAR (File no. 0032/2018/A1), the National Natural Science Foundation of China (Grant No.81873631, 81370866, 81070612) and the Guangzhou Science and technology planning project (Grant No.202002020047), NSFC-Guangdong United Fund (Grant No. 2020B1515120037).