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

Crit Care. 2021 Jan 28;25(1):39. doi: 10.1186/s13054-021-03476-x.

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / physiopathology
  • Aged
  • Chemokine CCL2 / analysis
  • Chemokine CCL2 / blood
  • Cytokines / metabolism*
  • Epidermal Growth Factor / analysis
  • Epidermal Growth Factor / blood
  • Female
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / blood
  • Interleukin-10 / analysis
  • Interleukin-10 / blood
  • Interleukin-1alpha / analysis
  • Interleukin-1alpha / blood
  • Interleukin-1beta / analysis
  • Interleukin-1beta / blood
  • Interleukin-2 / analysis
  • Interleukin-2 / blood
  • Interleukin-4 / analysis
  • Interleukin-4 / blood
  • Interleukin-6 / analysis
  • Interleukin-6 / blood
  • Male
  • Metabolic Clearance Rate / physiology*
  • Middle Aged
  • Peptide Fragments / analysis
  • Peptide Fragments / blood
  • Prospective Studies
  • Renal Replacement Therapy / methods
  • Sepsis / complications*
  • Sepsis / physiopathology
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Endothelial Growth Factors / analysis
  • Vascular Endothelial Growth Factors / blood

Substances

  • Chemokine CCL2
  • Cytokines
  • IL10 protein, human
  • IL4 protein, human
  • IL6 protein, human
  • Interleukin-1alpha
  • Interleukin-1beta
  • Interleukin-2
  • Interleukin-6
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factors
  • interferon gamma (1-39)
  • tumor necrosis factor (1-26)
  • Interleukin-10
  • Interleukin-4
  • Epidermal Growth Factor
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT03231748