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Abstract: FR-PO495

Glycosaminoglycan Modified-Dialysis Membranes Improve Blood Biocompatibility In Vitro

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Margalef, Maria, RIMLS, Radboud University Medical Centre, Nijmegen, Netherlands
  • Kim, Dooli, University of Twente - Faculty of Science and Technology, Enschede, Netherlands
  • Stamatialis, Dimitrios, University of Twente - Faculty of Science and Technology, Enschede, Netherlands
  • Van der vlag, Johan, RIMLS, Radboud University Medical Centre, Nijmegen, Netherlands
Background

The number of patients requiring renal replacement therapies is increasing with an estimated number of 5.4 million a year in 2030. Most patients use (hemo)dialysis (HD) therapy. Major drawbacks of HD are: (i) poor removal of toxic larger middle-sized molecules and protein-bound uremic solutes; (ii) large fluctuations in water balance and uremic waste, potassium and phosphate of the patients,since it is non-continuous (iii) not fit for prolonged use due to clogging and coagulation of the membranes. Recently, we showed in vitro that combining dialysis and adsorption in one step using mixed matrix membranes (MMM) improves removal of protein-bound uremic solutes from human plasma as compared to conventional dialysis membranes. Although the results with MMM are promising, for continuous use further optimization is required. Due to the well-known contribution of glycosaminoglycans (GAGs) to the barrier and anti-fouling properties of the natural filtration barrier in the kidney, this work aimed to improve hemo- and biocompatibility of MMM by application of novel GAGs either as coatings post membrane fabrication or by incorporation of the GAG into the membrane polymer via blending.

Methods

Flat MMM were coated or blended with the following GAG sources: Heparin, GAGs from porcine intestine (GPI), heparan sulphate (HS) isolated from cultured glomerular endothelial glycocalyx, HS from bovine kidney (HSBK), and heparinase III digested HSBK. Both GAG coating and blending showed a high stability on the MMM. Water permeance, and a panel of anti-coagulation and platelet adhesion assays were studied in all cases.

Results

The new MMM with 3 out of 5 GAGs have higher water permeance in comparison to non-modified MMM whereas heparin and GPI modified MMM were superior in their anti-coagulation and platelet adhesion properties.

Conclusion

GAG-modified MMM have superior biocompatible properties that may improve current dialysis treatment and ultimately enable incorporation into future portable artificial kidney devices.

Funding

  • Government Support - Non-U.S.