Comparison of Protein-Bound and Large Molecular-Weight Uremic Toxin Removals with Novel Super High-Flux Dialyzer between Hemodialysis (HD) and High-Volume Online Hemodiafiltration Modalities: A Cross-Over Randomized Controlled Study

Background: Protein-bound uremic toxins (PUBT) and large molecular weight uremic toxins (LMWT) are poorly removed by the standard hemodialysis (HD) using high-flux dialyzer (HF) and associated with long-term morbidity and mortality in end-stage kidney disease (ESKD) patients undergoing chronic HD. Two removal enhancing approaches including modality upgrade from HD to higher cost high-volume online hemodiafiltration (HDF) with HF or dialyzer upgrade from HF to novel super high-flux dialyzers (SHF) (such as ELISIO-21HX) with standard HD have been innovated and provide comparably improving both PUBT and LMWT removals. Whether the combined approaches, HDF using SHF, could yield additional benefit when compared with single approach, HD using SHF, were explored in the present crossover randomized controlled study. Methods: Fourteen ESKD patients treated with HDF using HF were included. After a run-in period, the patients were randomly allocated to receive either 8-week of HDF using SHF, ELISIO-21HX, or HD using SHF as the control treatment. After a wash-out period of HDF using HF, they were crossovered to receive the other treatment for 8 weeks. The removal capacities in-term of plasma reduction ratio (RR) of PBUT (free and total indoxyl sulfate, IS) and LMWT (β2-microglobulin, kappa and lambda free light chains) as well as the adverse albumin loss in dialysate were assessed. The 8-week longitudinal changes of these plasma parameters were also compared. Results: There was no significant reduction ratio between free and total indoxyl sulfate between SHF-HD and SHF-HDF at 8 weeks period. The reduction ratio of kappa and lambda free light chain were higher in SHF-HDF and kappa was more eliminated. There were no significant reduction ratio between β2-microglobulin and urea. There was no significant dialysate albumin loss (0.7 vs 1.2 g/session, P-value 0.14) between both groups and did not affect the serum albumin at 8th weeks. Conclusion: SHF-HD and SHF-HDF provided comparable PBUTs removal but higher large middle molecule uremic toxin reduction. SHF-HD might be the alternative treatment for PBUTs and LMWTs removals.SHF-HDF may be an option for further LMWT (i.e. kappa and lambda FLC) removal. Longer intervention and follow up period should be further conducted. Funding: Government Support – Non-U.S.