Clearance of Inflammatory Cytokines in Patients with Septic Acute Kidney Injury During Renal Replacement Therapy Using the EMiC2 Filter (Clic-AKI Study)

Abstract

BackgroundThe Ultraflux EMiC2 membrane is a high cutoff hemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous hemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance.MethodsThis was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-ƴ, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 hours after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, sieving coefficients (SCs), mass balances, and changes in serial serum concentrations.ResultsTwelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 hours (p<0.001). Apart from IL-4, IL-8 and MCP-1, the SCs of the cytokines were <0.6. The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-ƴ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-hour period. ConclusionEMiC2-CVVHD achieved modest removal of most cytokines by diffusion and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal.Trial registrationNCT03231748, registered on 27th July 2017