Altered serum metabolome associated with vascular calcification developed from CKD and the critical pathways

Introduction: Vascular calcification (VC) is more likely to be detected in the chronic kidney disease (CKD) population. The mechanism of VC development from CKD is different from that for simple VC and has always been a major research area. The aim of this study was to detect alterations in the metabolome during development of VC in CKD and to identify the critical metabolic pathways and metabolites involved in its pathogenesis. Methods: Rats in the model group were given an adenine gavage combined with a high-phosphorus diet to imitate VC in CKD. The aorta calcium content was measured and used to divide the model group into a VC group and non-vascular calcification group (non-VC group). The control group was fed a normal rat diet and given a saline gavage. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to determine the altered serum metabolome in the control, VC, and non-VC groups. The identified metabolites were mapped into the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (https://www.genome.jp/kegg/) for pathway and network analyses. Result: There were 14 metabolites that changed significantly in the VC group, with three metabolic pathways playing critical roles in the pathogenesis of VC in CKD: steroid hormone biosynthesis; valine, leucine and isoleucine biosynthesis; and pantothenate and CoA biosynthesis. Conclusion: Our results indicated changes in the expression of steroid sulfatase and estrogen sulfotransferase, and down-regulation of the in situ synthesis of estrogens in the VC group. In conclusion, the serum metabolome alters significantly during the pathogenesis of VC in CKD. The key pathways, metabolites, and enzymes we identified are worth further study and may become a promising therapeutic target for the treatment of VC in CKD.

Automated summary

The aim of this study was to detect alterations in the metabolome during development of vascular calcification (VC) in chronic kidney disease (CKD) and to identify the critical metabolic pathways and metabolites involved in its pathogenesis. The results showed that there were 14 significantly changed metabolites in the CKD VC group, with three metabolic pathways playing critical roles: steroid hormone biosynthesis, valine, leucine and isoleucine biosynthesis, and pantothenate and CoA biosynthesis. The study findings suggest changes in the expression of steroid sulfatase and estrogen sulfotransferase, and down-regulation of the in situ synthesis of estrogens in the VC group. These identified pathways, metabolites, and enzymes are worth further investigation as potential therapeutic targets for the treatment of VC in CKD.