Enhancing Cytokine Clearances with Sustained Low-Efficiency Diafiltration (SLED-f) Using High Cut-off Dialyzer in Septic AKI Patients: A Randomized Trial

Background: Hypercytokinemia contributes a major role in the pathogenesis and is associated with the high mortality in sepsisrelated acute kidney injury (AKI). Reductions of these cytokines have been reported to improve clinical outcomes. Online sustained low-efficiency diafiltration (SLED-f) using traditional high-flux (HF) dialyzer could remove some cytokines. Interestingly, the potential of enhancing cytokine removal by using newly designed high cut-off (HCO) dialyzer that could theoretically remove larger molecular weight solutes has never been studied in SLED-f before. Materials and Methods: The present randomized controlled trial was conducted in sepsis-related AKI patients to compare the efficacy of cytokine removal including interleukin (IL)-6, IL-8, IL-10, and tumor necrotic factor (TNF)-α by six-hour SLED-f between using HCO dialyzer (HCO-SLED-f, n = 8) and HF dialyzer (HF-SLED-f, n = 8). Results: HCO-SLED-f provided significantly higher clearances of TNF-α, IL-6, and IL-10 than HF-SLED-f. HCO-SLED-f demonstrated significant IL-8 and TNF-α reductions, (p=0.012 for both) after treatment whereas HF-SLED-f could only yield significant TNF-α reduction (p=0.018). The degree of all cytokine reductions did not show significant differences between both treatment groups. There were significantly higher total albumin losses in effluent fluid in HCO-SLED-f group than HF-SLED-f group, (p<0.001). The percentage of plasma albumin reduction was not different between both treatment groups. There were no significant differences in intra-dialytic blood pressure parameters during both treatments. Conclusion: In sepsis-related AKI, HCO-SLED-f could be safely applied and could enhance cytokine clearances as well as reduce more types of cytokines when compared with HF-SLED-f, although the degree of reduction did not show significant difference. The higher degree of albumin loss should be considered when using HCO-SLED-f. Trial registration: ClinicalTrials.gov, NCT03014232 Keywords: Sustained low-efficiency diafiltration (SLED-f), High cut-off dialyzer, Cytokines