A Novel Strategy for Enhanced Sequestration of Protein-Bound Uremic Toxins Using Smart Hybrid Membranes

Currently available hemodialysis (HD) membranes are unable to safely remove protein-bound uremic toxins (PBUTs), especially those bonded to human serum albumin (HSA). To overcome this issue, the prior administration of high doses of HSA competitive binders, such as ibuprofen (IBF), has been proposed as a complementary clinical protocol to increase HD efficiency. In this work, we designed and prepared novel hybrid membranes conjugated with IBF, thus avoiding its administration to end-stage renal disease (ESRD) patients. Two novel silicon precursors containing IBF were synthesized and, by the combination of a sol-gel reaction and the phase inversion technique, four monophasic hybrid integral asymmetric cellulose acetate/silica/IBF membranes in which silicon precursors are covalently bonded to the cellulose acetate polymer were produced. To prove IBF incorporation, methyl red dye was used as a model, thus allowing simple visual color control of the membrane fabrication and stability. These smart membranes may display a competitive behavior towards HSA, allowing the local displacement of PBUTs in future hemodialyzers.

[1]  Mónica Faria,et al.  Adsorption- and Displacement-Based Approaches for the Removal of Protein-Bound Uremic Toxins , 2023, Toxins.

[2]  S. Jokar,et al.  Interaction of Human Serum Albumin with Uremic Toxins: The Need of New Strategies Aiming at Uremic Toxins Removal , 2022, Membranes.

[3]  Mónica Faria,et al.  Novel Cellulose Acetate-Based Monophasic Hybrid Membranes for Improved Blood Purification Devices: Characterization under Dynamic Conditions , 2021, Membranes.

[4]  V. Maheshwari,et al.  Removal of Protein-Bound Uremic Toxins Using Binding Competitors in Hemodialysis: A Narrative Review , 2021, Toxins.

[5]  Nuno Marques de Almeida,et al.  Improving hydraulic permeability, mechanical properties, and chemical functionality of cellulose acetate-based membranes by co-polymerization with tetraethyl orthosilicate and 3-(aminopropyl)triethoxysilane. , 2021, Carbohydrate polymers.

[6]  V. Semião,et al.  The effect of ultrafiltration transmembrane permeation on the flow field in a surrogate system of an artificial kidney , 2021, Experimental Results.

[7]  A. Abdelrasoul,et al.  Protein-bound uremic toxins (PBUTs) in chronic kidney disease (CKD) patients: Production pathway, challenges and recent advances in renal PBUTs clearance. , 2021, NanoImpact.

[8]  M. N. de Pinho,et al.  Challenges of reducing protein-bound uremic toxin levels in chronic kidney disease and end stage renal disease. , 2020, Translational research : the journal of laboratory and clinical medicine.

[9]  P. Brogueira,et al.  Hybrid flat sheet cellulose acetate/silicon dioxide ultrafiltration membranes for uremic blood purification , 2020, Cellulose.

[10]  L. G. Vu,et al.  Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017 , 2020, The Lancet.

[11]  P. Brogueira,et al.  Hybrid Integral Asymmetric Cellulose Acetate/Silicon Dioxide Ultrafiltration Membranes for Uremic Blood Purification , 2019, IFMBE Proceedings.

[12]  V. Maheshwari,et al.  Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding Competitor. , 2019, Clinical journal of the American Society of Nephrology : CJASN.

[13]  A. Carvalho,et al.  Structure of water in hybrid cellulose acetate-silica ultrafiltration membranes and permeation properties. , 2018, Carbohydrate polymers.

[14]  H. Krum,et al.  Protein-bound uremic toxins: a long overlooked culprit in cardiorenal syndrome. , 2016, American journal of physiology. Renal physiology.

[15]  M. Henrie,et al.  Improved dialytic removal of protein-bound uraemic toxins with use of albumin binding competitors: an in vitro human whole blood study , 2016, Scientific Reports.

[16]  N. Levin,et al.  Enhanced Indoxyl Sulfate Dialyzer Clearance with the Use of Binding Competitors , 2015, Blood Purification.

[17]  B. Pruitt,et al.  Nanomechanical actuation of a silicon cantilever using an azo dye, self-assembled monolayer. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[18]  R. Vanholder,et al.  Review of Protein-Bound Toxins, Possibility for Blood Purification Therapy , 2013, Blood Purification.

[19]  Z. Massy,et al.  Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. , 2009, Clinical journal of the American Society of Nephrology : CJASN.

[20]  C. Wanner,et al.  PROGRESS IN UREMIC TOXIN RESEARCH: The Role of EUTox in Uremic Toxin Research , 2009, Seminars in dialysis.

[21]  R. Tacke,et al.  Pentacoordinate Silicon Compounds with SiO5 Skeletons Containing SiOH or SiOSi Groups: Derivatives of the Pentahydroxosilicate(1−) Anion [Si(OH)5]- and Its Anhydride [(HO)4Si−O−Si(OH)4]2- , 2000 .

[22]  M J Lysaght,et al.  Effect of membrane composition and structure on solute removal and biocompatibility in hemodialysis. , 1999, Kidney international.

[23]  D Luehmann,et al.  Technical requirements for rapid high-efficiency therapies. , 1986, Artificial organs.

[24]  H. Strathmann,et al.  The formation mechanism of phase inversion membranes , 1977 .

[25]  M. Mineshima The past, present and future of the dialyzer. , 2015, Contributions to nephrology.

[26]  J. Vienken,et al.  Cellulose carbamates and derivatives as hemocompatible membrane materials for hemodialysis. , 1999, Artificial organs.