Multi-Omics Analysis of PBMCs Revealed Distinct Biological Differences Between Hemodialysis and Peritoneal Dialysis

Although the clinical differences between hemodialysis (HD) and peritoneal dialysis (PD) are well established, the specific biological mechanisms underlying these differences remain incompletely understood. We performed untargeted proteomic and transcriptomic analyses of peripheral blood mononuclear cells (PBMCs) from healthy controls (CTRs) and patients with chronic kidney disease undergoing HD or PD. Key findings were validated in an independent cohort using standardized biomolecular techniques. Bioinformatic analysis identified 36 differentially expressed proteins and 19 transcripts between HD and PD according to the predefined FDR-adjusted significance threshold. Functional enrichment analysis revealed that these factors were primarily involved in cellular senescence, aging, and stress-response pathways. Among the identified molecules, interferon regulatory factor 8 (IRF8) was the only factor consistently upregulated in HD compared with PD in both omics analyses. This finding was confirmed by ELISA in an independent cohort (p < 0.0001). Kinase enrichment analysis prioritized Checkpoint Kinase 2 (CHEK2), which was also identified by proteomics, as a predicted upstream regulator and warrants further investigation. Overall, these findings identify distinct molecular signatures in PBMCs from HD and PD patients and suggest a potential association between HD and increased PBMC IRF8 abundance and a senescence-related signature, which requires validation in larger and longitudinal cohorts.