SuO005
CHARACTERIZATION OF THE TRANSCRIPTOMIC PROFILE OF PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMCS) IN PATIENTS TREATED WITH ONLINE-HEMODIAFILTRATION (OL- HDF)

Introduction and Aims: Several clinical studies suggest that OL-HDF can reduce the progression of dialysis-related cardiovascular diseases, but the molecular mechanisms underlying this improvement are not yet known. The aim of this study was to identify, through a high-throughput approach, differences in the gene expression profile of PBMCs from patients undergoing OL-HDF or bicarbonate dialysis (BHD).

Methods: The gene expression profiles were evaluated in PBMCs isolated from 12 patients regularly dialyzed with OL-HDF (reinfusion>18L) and 12 patients treated with BHD, through SurePrint G3 Human Gene Expression 60K Microarray Kit (Agilent Technologies). The results were evaluated by statistical (unpaired t test, correction for multiple testing Benjamini-Hochberg) and functional analysis (Ingenuity Pathway Analysis, IPA).

Results: Setting a fold change>1.5, we observed that 868 genes were differentially expressed in the comparison between OL-HDF and BHD. Two-D Hierarchical clustering and Principal Component Analysis (PCA) revealed a complete separation of the two patients’ groups based on the expression profiles of the differentially expressed genes. IPA analysis revealed that among the most significant tox functions modulated by OL-HDF there were cardiac damage (p=0.003), hypertrophy (p=0.002), degeneration (p=0.001) and arteriopathy (p=0.002). The main canonical pathways influenced by OL-HDF included cholesterol biosynthesis (p=0.0004). The differentially expressed genes were included in 25 functional networks. Two of the top networks were correlated with inflammatory response (genes included 23, IPA score 19), immune cell trafficking (genes included 20, IPA score 17) and cardiovascular disease (genes included 17, IPA score 15).

Conclusions: Our data suggest that the OL-HDF can contribute to cardiovascular risk reduction through the modulation of pathways involved in inflammation, progression of atherosclerotic disease and cardiac dysfunction. This observation could open new perspectives in the prevention of cardiovascular risk in dialysis.