Clearance of inflammatory cytokines in patients with septic acute kidney injury during renal replacement therapy using the EMiC2 filter (Clic-AKI study)

Nuttha Lumlertgul, Anna Hall, Luigi Camporota, Siobhan Crichton, Marlies Ostermann, Nuttha Lumlertgul, Anna Hall, Luigi Camporota, Siobhan Crichton, Marlies Ostermann

Abstract

Background: The EMiC2 membrane is a medium cut-off haemofilter (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 haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance.

Methods: This 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)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, 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 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations.

Results: Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, 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-h period.

Conclusion: EMiC2-CVVHD achieved modest removal of most cytokines 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 registration: NCT03231748, registered on 27th July 2017.

Keywords: Acute kidney injury; CRRT; EMiC2 filter; Extracorporeal blood purification; High cut-off; Kidney replacement therapy; Middle cut-off; Removal; Sepsis.

Conflict of interest statement

Dr. Ostermann has received speaker honoraria and research funding from Fresenius Medical. All other authors declare no conflicts of interests.

Figures

Fig. 1
Fig. 1
Cytokine plasma concentrations expressed as a percentage of the concentration at time = 0 h. a Mean and standard error of interleukin-2 (IL-2), IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF) concentrations. b Mean and standard error of interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), epidermal growth factor (EGF)
Fig. 2
Fig. 2
The median levels of total amount of cytokine moved (Mt), expressed as a percentage of the inlet mass rate (%Mt/Mi) at t = 1, 6, 24, and 48 h after continuous veno-venous haemodialysis initiation (connected line). For each time point, the relative proportions of adsorption (%Mad/Mi, gray bars) and haemofilter clearance (%Mdf/Mi, dotted bars) are shown. a IL-2, b IL-4, c IL-6, d IL-8, e IL-10, f VEGF, g IFN-γ, h TNF-α, i IL-1α, j IL-1β, k MCP-1, l EGF

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