Abstract

Objective: End-Stage Renal Disease (ESRD) can increase the risk of Cardiovascular disease (CV). We aimed to investigate the pathways and mechanisms associated with potential protective genes linked to CV (CVP).

Methods: We conducted a systematic bioinformatics analysis using publicly available datasets from the Gene Expression Omnibus (GEO). Differentially Expressed Genes (DEGs) were identified in patients with ESRD with and without arrhythmia using stringent statistical criteria. Functional enrichment analyses were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways to elucidate the biological roles of these DEGs. The identified biomarker expression levels were verified by employing RT-qPCR with clinical samples.

Results: Our analysis revealed a distinct set of DEGs in ESRD patients with arrhythmia compared to those without arrhythmia. GO and KEGG pathway analyses indicated that these DEGs were involved in key biological processes and pathways relevant to cardiovascular disorders and renal function, including wound healing, platelet activation, and fluid-level regulation. Moreover, this study identified four downregulated genes (ABLIM3, TREML1, VCL and AVPR1A) and two upregulated genes (BHLHA15 and FZD8), which exhibited significant alterations in expression levels, with some showing robust discriminatory power, as evidenced by high Area Under the Curve (AUC) values in Receiver Operating Characteristic (ROC) curve analysis for predicting patients without CV risks. Finally, the expression of these identified genes in clinical samples was validated by RT-qPCR, which was consistent with the result of public database.

Conclusion: We found significant expression changes and high discriminatory power for predicting CV risk among patients with ESRD. This study highlights these genes' potential as biomarkers and therapeutic targets, providing new insights into the molecular mechanisms linking ESRD and arrhythmia, and paving the way for improved patient outcomes

Keywords: End stage renal disease; ESRD; Arrhythmias; circRNA; Gene expression omnibus