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

Maurizio Bruschi, Simona Granata, Silvia Lai, Valentina Pistolesi, Laura Barberio, Rossana D'Agostino, Francesca Sorace, Francesca Giordano, Paola Pontrelli, Loreto Gesualdo, Lida Tartaglione, Giovanni Candiano, Sonia Spinelli, Andrea Petretto, Chiara Lavarello, Edoardo La Porta, Michele Provenzano, Gianluigi Zaza

Journal: International journal of molecular sciences 2026;27(16):

PMID: 42653471

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Abstract

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.

Address: Laboratory of Molecular Nephrology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, 16147 Genoa, Italy.; Department of Experimental Medicine (DIMES), University of Genoa, 16126 Genoa, Italy.; Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy.; Nephrology, Dialysis and Transplantation Unit, Policlinico Riuniti University Hospital, 71122 Foggia, Italy.; Nephrology, Dialysis and Transplantation Unit, Department of Translational and Precision Medicine, Sapienza University of Rome-Policlinico Umberto I, 00185 Rome, Italy.; Nephrology, Dialysis and Transplantation Unit, Policlinico Umberto I, 00161 Rome, Italy.; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.; Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy.; Laboratory of Molecular Nephrology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, 16147 Genoa, Italy.; Core Facility for Omics Sciences, IRCCS Istituto Giannina, 16147 Genoa, Italy.; Nephrology, Dialysis and Transplantation Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, 16147 Genoa, Italy.; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.; Division of Nephrology, Dialysis and Transplantation, Annunziata Hospital, 87100 Cosenza, Italy.

DOI: 10.3390/ijms27167470

MeSH Terms: Humans, Peritoneal Dialysis, Leukocytes, Mononuclear, Renal Dialysis, Interferon Regulatory Factors, Proteomics, Female, Interferon Regulatory Factor-8, Male, Multiomics, Middle Aged, Renal Insufficiency, Chronic, Gene Expression Profiling, Proteome, Aged, Transcriptome, Cellular Senescence