Transcriptomic analysis identified novel biomarkers and therapeutic targets in CKD transition to ESRD

Lin Zhu¹Ying Liu¹Shen Jie¹Fan Ping²Jun Xu³Kai Qu^2*Xia Shen^1*

• ¹Shaanxi University of Chinese Medicine, Xianyang, China
• ²Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, China
• ³Cardiovascular and Cerebrovascular Drugs Research and Development Center, Tianjin Institute of Medical and Pharmaceutical Sciences, Tianjin, China

Background: In the general population, the transition of chronic kidney disease (CKD) to stage 5 CKD (end-stage renal disease, ESRD) is an important cause of death in patients. The aim of this study was to identify new biomarkers to help prevent and diagnose CKD transition.Methods: Differential expression analysis and weighted correlation network analysis (WGCNA) were applied to screen for genes that were highly associated with CKD and ESRD. The cytoHubba plugins were used to determine the key genes in the PPI network. GO and KEGG analyses were performed to reveal the functions and pathways associated with CKD transition. Subsequently, in the other CKD and ESRD datasets. A total of 4 datasets were analyzed in this study to ensure the robustness and generalizability of our findings. The key genes were verified using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB), and their diagnostic value was assessed using receiver operating characteristic (ROC) curves.Results: The 10 key genes that were identified were EPB42, KLF1, H3F3A, RPS11, ANK1, PRMT6, EP300, GLTSCR2, RXRB, and MYSM19. Reduced blood oxygen-carrying capacity, mitochondrial dysfunction, reduced muscle mass, and inflammation were found to be strongly associated with CKD transition; among the 10 key genes, EPB42, KLF1, and H3F3A were related with oxygen-carrying capacity and inflammation. Notably, EPB42 expression showed good diagnostic ability, with decreased level during CKD and increased level during ESRD.Conclusions: Through the integrative analysis of CKD and ESRD datasets, this study has provided insights into the functional features underlying the transition from CKD to ESRD. These findings not only enhance our understanding of the pathophysiological mechanisms involved in CKD transition but also have significant clinical implications.Specifically, the identification of potential therapeutic targets and biomarkers may facilitate the development of more effective interventions to delay or prevent the transition of CKD to ESRD.