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Thrombogenicity and long-term cytokine removal capability of a novel asymmetric triacetate membrane hemofilter

  • Original Article
  • Biomaterials
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Abstract

Hemofilters applied in continuous renal replacement therapies (CRRTs) for the treatment of acute kidney injury must meet high standards in biocompatibility and permeability for middle and large molecules over extended treatment times. In general, cellulose-based membranes exhibit good biocompatibility and low fouling, and thus appear to be beneficial for CRRT. In this in vitro study, we compared a novel asymmetric cellulose triacetate (ATA) membrane with three synthetic membranes [polysulfone (PS), polyethersulfone (PES), and polyethylenimine-treated acrylonitrile/sodium methallyl sulfonate copolymer (AN69 ST)] regarding thrombogenicity and cytokine removal. For thrombogenicity assessment, we analyzed the thrombin–antithrombin complex (TAT) generation in human whole blood during 5 h recirculation and filtration. Sieving coefficients of interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) were determined using human plasma as test fluid. ATA and AN69 ST membrane permeability were determined also during long-term experiments (48.5 h). ATA exhibited the lowest TAT generation (6.3 µg/L at 5 h), while AN69 ST induced a pronounced concentration increase (152.1 µg/L) and filter clogging during 4 out of 5 experiments. ATA (IL-8: 1.053; IL-6: 1.079; IL-10: 0.898; TNF-α: 0.493) and PES (0.973; 0.846; 0.468; 0.303) had the highest sieving coefficients, while PS (0.697; 0.100; 0.014; 0.012) and AN69 ST (N/A; 0.717; 0; 0.063) exhibited lower permeability. Long-term experiments revealed stronger fouling of the AN69 ST compared to the ATA membrane. We observed the highest permeability for the tested cytokines, the lowest thrombogenicity, and the lowest fouling with the ATA membrane. In CRRT, these factors may lead to increased therapy efficacy and lower incidence of coagulation-associated events.

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Acknowledgements

The authors gratefully acknowledge excellent experimental work by Fanny Doss. Part of this work was financially supported by a grant from the Ministry of Education, Science and Culture of the State of Mecklenburg-Vorpommern (Grant number AU 15 002).

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Authors and Affiliations

  1. Extracorporeal Immunomodulation Unit, Fraunhofer Institute for Cell Therapy and Immunology, Schillingallee 68, Room 1.06, 18057, Rostock, Germany

    Andreas Körtge, Thomas Wild, Benjamin Heskamp, Manuel Folk, Steffen Mitzner & Reinhold Wasserkort

  2. Division of Nephrology, Centre for Internal Medicine, University Medicine Rostock, Rostock, Germany

    Steffen Mitzner

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  1. Andreas Körtge
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  2. Thomas Wild
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  3. Benjamin Heskamp
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  4. Manuel Folk
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  5. Steffen Mitzner
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  6. Reinhold Wasserkort
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Correspondence to Andreas Körtge.

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Conflict of interest

The study was financially supported by Nipro Corporation. ATA membrane (SOLACEA™-HF) and PES membrane hemofilters (ELISIO™-HF) were provided by Nipro Corporation. Otherwise, the authors declare that they have no conflicts of interest. The results presented in this paper have not been published previously.

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Körtge, A., Wild, T., Heskamp, B. et al. Thrombogenicity and long-term cytokine removal capability of a novel asymmetric triacetate membrane hemofilter. J Artif Organs 21, 435–442 (2018). https://doi.org/10.1007/s10047-018-1062-1

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  • DOI: https://doi.org/10.1007/s10047-018-1062-1

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