Transcriptomic Profiling of Peripheral Blood Mononuclear Cells Reveals Key Molecular Signatures in Chronic Kidney Disease Patients with Heart Failure

BackgroundHeart failure (HF) is a frequent and severe complication among patients with chronic kidney disease (CKD), particularly in advanced stages and end stage renal disease (ESRD). This study focuses on understanding the molecular interplay between CKD and HF beyond the context of maintenance hemodialysis (MHD). Given that peripheral blood mononuclear cells (PBMCs) reflect systemic inflammatory and transcriptional alterations, we analyzed PBMC transcriptomes to uncover potential biomarkers and mechanistic links connecting CKD and HF. MethodsPublicly available RNA Seq data comprising PBMCs from 15 CKD patients with HF (SRX23265333) and 14 healthy controls (SRX19031772) were analyzed. Quality control was performed using FastQC and Fastp, followed by alignment to the human reference genome with HISAT2. Gene counts were normalized, and differential expression was determined using DESeq2. Functional enrichment analyses (Gene Ontology and KEGG) identified key biological pathways. Protein protein interaction (PPI) networks were constructed using STRING, and hub genes were validated through disease and gene associations in the Comparative Toxicogenomics Database (CTD). ResultsDifferential expression analysis revealed several genes significantly dysregulated in CKD patients with HF compared to controls. Enrichment results highlighted processes associated with extracellular matrix remodeling, immune activation, and cardiac renal fibrosis. PPI analysis identified four major hub genes CCL2, ALB, EGFR, and COL1A2 as central nodes within the network. These genes are functionally linked to inflammatory signaling, vascular remodeling, and fibrotic progression, consistent with pathophysiological mechanisms of HF and CKD. CTD validation further confirmed their association with cardiorenal dysfunction. DiscussionThis integrative transcriptomic study identifies CCL2, ALB, EGFR, and COL1A2 as key PBMC expressed hub genes linking CKD and HF. The findings enhance understanding of the molecular basis of cardiorenal syndrome and propose candidate biomarkers and therapeutic targets for future translational research.