Multi-omics analysis of PBMCs revealed distinct molecular signatures between hemodialysis and peritoneal dialysis patients, with interferon regulatory factor 8 (IRF8) consistently upregulated in HD compared with PD in both proteomic and transcriptomic analyses, suggesting a potential association between HD and a senescence-related signature.
Key Findings
Results
Untargeted proteomic and transcriptomic analyses identified 36 differentially expressed proteins and 19 transcripts between HD and PD patients.
Analyses were performed on peripheral blood mononuclear cells (PBMCs) from healthy controls (CTRs) and patients with chronic kidney disease undergoing HD or PD.
Bioinformatic analysis used a predefined FDR-adjusted significance threshold to identify differentially expressed molecules.
Both proteomic (untargeted) and transcriptomic approaches were applied to the same sample types.
Results
Functional enrichment analysis revealed that differentially expressed factors between HD and PD were primarily involved in cellular senescence, aging, and stress-response pathways.
These pathways were identified through bioinformatic functional enrichment analysis of the 36 proteins and 19 transcripts.
The findings suggest distinct biological mechanisms underlie the clinical differences between the two dialysis modalities.
Senescence-related signatures were a prominent feature distinguishing HD from PD at the molecular level.
Results
Interferon regulatory factor 8 (IRF8) was the only molecule consistently upregulated in HD compared with PD in both omics analyses.
IRF8 was identified as upregulated in both the proteomic and transcriptomic datasets.
This finding was validated by ELISA in an independent cohort (p < 0.0001).
IRF8 was described as the only factor meeting consistency criteria across both omics platforms.
Results
Kinase enrichment analysis prioritized Checkpoint Kinase 2 (CHEK2) as a predicted upstream regulator of the differentially expressed molecules in HD versus PD.
CHEK2 was also independently identified by proteomics analysis.
The authors note that CHEK2 'warrants further investigation' as an upstream regulator.
CHEK2 is known to be involved in DNA damage response and senescence-related pathways.
Conclusions
The study identified distinct molecular signatures in PBMCs from HD and PD patients, suggesting biological differences beyond what is clinically established.
Key findings were validated in an independent cohort using standardized biomolecular techniques including ELISA.
The authors note that validation in 'larger and longitudinal cohorts' is required.
Although clinical differences between HD and PD are well established, 'the specific biological mechanisms underlying these differences remain incompletely understood.'
What This Means
This research suggests that patients on two common types of kidney dialysis — hemodialysis (HD, where blood is filtered by a machine) and peritoneal dialysis (PD, where filtering occurs inside the abdomen) — show meaningful biological differences at the cellular and molecular level, beyond what doctors already observe clinically. By analyzing immune cells (PBMCs) from dialysis patients and healthy individuals using two complementary molecular techniques (proteomics and transcriptomics), the researchers identified 36 proteins and 19 gene transcripts that were expressed differently between HD and PD patients. These differences were linked to biological processes involving cellular aging, stress responses, and a phenomenon called cellular senescence, where cells stop dividing but remain active and can drive inflammation.
The most notable finding was that a protein called IRF8 (interferon regulatory factor 8) was consistently higher in HD patients compared to PD patients in both molecular analyses, and this was confirmed with a separate blood test (ELISA) in an additional group of patients with very high statistical confidence (p < 0.0001). IRF8 plays a role in immune regulation, and its elevated levels in HD patients may reflect greater immune stress or accelerated cellular aging associated with that treatment modality. Another molecule, CHEK2, a kinase involved in DNA damage responses, was flagged as a likely upstream controller of these molecular differences.
This research suggests that HD and PD do not just differ in how they physically clean the blood — they may also create fundamentally different biological environments within patients' immune cells, particularly related to aging and stress pathways. These findings could eventually help explain why some patients on different dialysis types have different long-term health outcomes, and may point toward new targets for monitoring or intervention, though the authors caution that larger and longer-term studies are needed to confirm these results.
Bruschi M, Granata S, Lai S, Pistolesi V, Barberio L, D'Agostino R, et al.. (2026). Multi-Omics Analysis of PBMCs Revealed Distinct Biological Differences Between Hemodialysis and Peritoneal Dialysis.. International journal of molecular sciences. https://doi.org/10.3390/ijms27167470