Exploring the Impact of Expanded Hemodialysis with Super-High-Flux Dialyzer on Inflammation and Gene Expression: A Prospective Cohort Study in Prevalent Hemodialysis Patients

INTRODUCTION: End-stage kidney disease (ESKD) features chronic inflammation and immune dysregulation. The effects of long-term expanded hemodialysis (HDx) using a super-high-flux (SHF) dialyzer on peripheral blood mononuclear cell (PBMC) transcriptomes and circulating inflammatory markers are unclear. METHODS: In a single-center pilot study, 10 prevalent hemodialysis patients were evaluated at baseline on standard high-flux hemodialysis and after 12 months on high-efficiency HDx delivered with an SHF dialyzer (ELISIO-17Hx; Nipro, Osaka, Japan). PBMC RNA sequencing was performed by Macrogen (Seoul, South Korea). Serum cytokines/chemokines were quantified by bead-based multiplex immunoassay on the Luminex xMAP platform (MILLIPLEX; Merck, Darmstadt, Germany). Differential expression controlled the false-discovery rate; paired tests compared biomarker levels. RESULTS: Out of 43 genes analyzed, 12 showed significant upregulation. TNF and CCL4 genes were notably altered after 12 months of HDx (adjusted p = 0.037 and p = 0.025). Serum levels of pro-inflammatory markers - TNF-α, CCL4, CCL2, and MMP-9 - significantly declined, while IL-10 increased (p < 0.001). Specific changes included TNF-α (31.5 [29.2-35.2] to 26.9 [23.7-30.9] pg/mL; p = 0.028), CCL4 (32.5 ± 14.1 to 22.7 ± 8.2 pg/mL; p = 0.015), CCL2 (489.6 ± 97.0 to 319.6 ± 103.5 pg/mL; p < 0.001), and MMP-9 (5,241.5 [4,432.3-19,709.3] to 555.6 [202.0-709.3] pg/mL; p = 0.005). IL-10 increased from 2.80 ± 1.86 to 5.15 ± 2.10 pg/mL (p = 0.001). TNF-β showed a nonsignificant change (mean difference -2.4; p = 0.101). Other markers remained unchanged. CONCLUSION: ESKD shows PBMC upregulation of TNF and CCL4, whereas 12-month high-efficiency HDx lowers circulating TNF-α, CCL4, CCL2, and MMP-9. This transcriptome-serum discordance highlights immune dysregulation, while HDx appears to attenuate inflammation; the shift toward anti-inflammatory signals suggests potential clinical benefit.