Clearance of Selected Plasma Cytokines with Continuous Veno-Venous Hemodialysis Using Ultraflux EMiC2 versus Ultraflux AV1000S

Abstract

Background: High cutoff hemofilters might support the restoration of immune homeostasis in systemic inflammation by depleting inflammatory mediators from the circulation. Methods: Interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha depletion was assessed in 30 sepsis patients with acute renal failure using continuous veno-venous hemodialysis with high cutoff versus standard filters (CVVHD-HCO vs. CVVHD-STD) over 48 h. Results: The transfer of IL-6 and IL-8 was significantly higher for CVVHD-HCO, as shown by increased IL-6 and IL-8 effluent concentrations. The mean plasma cytokine concentrations decreased over time for all cytokines without detectable differences for the treatment modalities. No transfer of albumin was observed for either of the filters. C-reactive protein remained stable over time and did not differ between CVVHD-HCO and CVVHD-STD, while procalcitonin decreased significantly over 48 h for both treatment modalities. Conclusion: CVVHD-HCO achieved enhanced removal of IL-6 and IL-8 as compared to CVVHD-STD, without differentially reducing plasma cytokine levels.

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

“…Previous studies explored cytokine changes and cytokine removal by the EMiC2 filter, but none have fully investigated the various mechanisms of cytokine clearance in critically ill patients with sepsis [19][20][21][22]. Despite reported decent removal of IL-6, IL-8, IL-1β, and TNF-α (MW 8.4 to 25 kDa) in-vitro, the effluent clearance rates varied markedly in humans [20,21,37]. Our data show that the majority of cytokines did not achieve high SCs apart from IL-8, IL-4 and MCP-1.…”

“…Some of our findings are compatible with data in the literature but not all. For instance, a previous study demonstrated higher IL-6 and IL-8 clearance by the EMiC2 filter than the standard membrane, but showed no difference in plasma cytokine decline over time [20]. Another study showed comparable IL-6 clearance between the EMiC2 and high-flux membrane [21].…”

“…molecular size, protein binding, and filter porosity. Sieving coefficients are calculated using the following equation [20]:…”

“…Case reports showed reduction in serum k-free light chains and myoglobin levels with the EMiC2 filter but actual removal by the filter was not investigated [14][15][16][17]. Other studies reported higher removal of kappa light chains (23kDa), β2microglobulin (17kDa), myoglobin (17kDa), IL-6, and IL-8 in patients receiving treatment with EMiC2 filters compared with standard high-flux membranes [18][19][20][21]. Continuous veno-venous hemodialysis (CVVHD) using the EMiC2 filter was well tolerated and albumin loss was limited [22].…”

“…Furthermore, the causal link between reduction of plasma cytokine concentration and extracorporeal cytokine removal has not been demonstrated [20,22]. Before proceeding to a trial comparing the EMiC2 filter with other commercially available filters to manage sepsis-associated AKI, it is important to determine the characteristics and the actual magnitude of cytokine removal in vivo.…”