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Review

Removal of Protein-Bound Uremic Toxins Using Binding Competitors in Hemodialysis: A Narrative Review

1
Renal Research Institute, New York, NY 10065, USA
2
Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
*
Author to whom correspondence should be addressed.
Toxins 2021, 13(9), 622; https://doi.org/10.3390/toxins13090622
Received: 9 August 2021 / Revised: 28 August 2021 / Accepted: 31 August 2021 / Published: 4 September 2021
(This article belongs to the Special Issue New Strategies for the Reduction of Uremic Toxins)
Removal of protein-bound uremic toxins (PBUTs) during conventional dialysis is insufficient. PBUTs are associated with comorbidities and mortality in dialysis patients. Albumin is the primary carrier for PBUTs and only a small free fraction of PBUTs are dialyzable. In the past, we proposed a novel method where a binding competitor is infused upstream of a dialyzer into an extracorporeal circuit. The competitor competes with PBUTs for their binding sites on albumin and increases the free PBUT fraction. Essentially, binding competitor-augmented hemodialysis is a reactive membrane separation technique and is a paradigm shift from conventional dialysis therapies. The proposed method has been tested in silico, ex vivo, and in vivo, and has proven to be very effective in all scenarios. In an ex vivo study and a proof-of-concept clinical study with 18 patients, ibuprofen was used as a binding competitor; however, chronic ibuprofen infusion may affect residual kidney function. Binding competition with free fatty acids significantly improved PBUT removal in pre-clinical rat models. Based on in silico analysis, tryptophan can also be used as a binding competitor; importantly, fatty acids or tryptophan may have salutary effects in HD patients. More chemoinformatics research, pre-clinical, and clinical studies are required to identify ideal binding competitors before routine clinical use. View Full-Text
Keywords: binding competition; hemodialysis; intoxication; indoxyl sulfate; p-cresyl sulfate; CMPF binding competition; hemodialysis; intoxication; indoxyl sulfate; p-cresyl sulfate; CMPF
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MDPI and ACS Style

Maheshwari, V.; Tao, X.; Thijssen, S.; Kotanko, P. Removal of Protein-Bound Uremic Toxins Using Binding Competitors in Hemodialysis: A Narrative Review. Toxins 2021, 13, 622. https://doi.org/10.3390/toxins13090622

AMA Style

Maheshwari V, Tao X, Thijssen S, Kotanko P. Removal of Protein-Bound Uremic Toxins Using Binding Competitors in Hemodialysis: A Narrative Review. Toxins. 2021; 13(9):622. https://doi.org/10.3390/toxins13090622

Chicago/Turabian Style

Maheshwari, Vaibhav, Xia Tao, Stephan Thijssen, and Peter Kotanko. 2021. "Removal of Protein-Bound Uremic Toxins Using Binding Competitors in Hemodialysis: A Narrative Review" Toxins 13, no. 9: 622. https://doi.org/10.3390/toxins13090622

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