Improving immune function and mitochondrial health in patients undergoing hemodialysis: benefits of combining high-flux dialysis with hemoperfusion

Objective This study aimed to investigate the effects of combining hemoperfusion (HP) with high-flux hemodialysis (HFD) on T lymphocyte subsets, mitochondrial health, and clinical outcomes in patients undergoing maintenance hemodialysis (MHD). Methods In this single-center, prospective, self-controlled trial, 20 MHD patients received their regular HFD treatment, with the addition of a single HP session every 2 weeks for 12 sessions. Levels of protein-bound uremic toxins (PBUTs: indoxyl sulphate [IS] and p-cresyl sulphate [PCS]), T lymphocyte subsets (CD3+, CD4+, CD8+), mitochondrial membrane potential (MMP) in T cells, and patient-reported outcomes (SF-36, PSQI, pruritus scale) were assessed before and after the 12 sessions intervention. Results Following a single HP + HFD session, IS and PCS levels decreased significantly ( p < 0.001). However, their pre-perfusion levels at end were not significantly different from baseline. After 12 sessions, increases were observed in the levels of CD3+, CD4+, CD8 + cells, the CD4+/CD8 + ratio, and the percentages of CD3 + MMP, CD4 + MMP, and CD8 + MMP (all p < 0.05). Patients also demonstrated significant improvements in sleep quality (PSQI), uremic pruritus, and overall quality of life (SF-36) (all p < 0.01). Additionally, serum phosphorus and parathyroid hormone levels were significantly reduced after the treatment period. Conclusion After 12 sessions of combined hemoperfusion and high-flux dialysis, we observed significant increases in T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8 + ratio) and the percentage of T cells with preserved mitochondrial membrane potential. Patients also reported improved sleep quality, reduced pruritus, and better quality of life. However, pre-dialysis levels of protein-bound uremic toxins (indoxyl sulphate and p-cresyl sulphate) of last session were not significantly different from baseline, despite effective clearance immediately after each combined session. Therefore, the observed improvements in immune-related parameters cannot be mechanistically attributed to a sustained reduction in these toxins. Alternative explanations—such as intermittent attenuation of peak toxin concentrations, clearance of unmeasured solutes, or non-specific effects—remain possible. Given the single-arm, observational design, these findings are hypothesis-generating and require confirmation in randomized controlled trials.