Enhanced Indoxyl Sulfate Dialyzer Clearance with the Use of Binding Competitors

Tao, Xia; Thijssen, Stephan; Levin, Nathan W.; Kotanko, Peter; Handelman, Garry J.

doi:10.1159/000381008

Cited by 26 publications

(21 citation statements)

References 51 publications

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“…The added convective component of hemodiafiltration adds only little beyond the PBUT removal achieved in standard high-flux HD 13 , 14 . Additional approaches to remove PBUTs also exist, notably (i) adsorption of toxins during dialysis on mixed-matrix membranes 15 or on adsorbent zeolite silicalite 16 , (ii) maintaining the diffusive gradient across the dialyzer fiber by circulating albumin 17 or activated charcoal in the dialysate 18 , (iii) displacing PBUTs from albumin using binding competitors to increase the free toxin fraction 19 , 20 , and (iv) weakening the toxin affinity for albumin using a high-frequency electromagnetic field 21 .…”

Section: Introductionmentioning

confidence: 99%

A novel mathematical model of protein-bound uremic toxin kinetics during hemodialysis

Maheshwari

Thijssen

Fuertinger

et al. 2017

Sci Rep

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Protein-bound uremic toxins (PBUTs) are difficult to remove by conventional hemodialysis; a high degree of protein binding reduces the free fraction of toxins and decreases their diffusion across dialyzer membranes. Mechanistic understanding of PBUT kinetics can open new avenues to improve their dialytic removal. We developed a comprehensive model of PBUT kinetics that comprises: (1) a three-compartment patient model, (2) a dialyzer model. The model accounts for dynamic equilibrium between protein, toxin, and the protein-toxin complex. Calibrated and validated using clinical and experimental data from the literature, the model predicts key aspects of PBUT kinetics, including the free and bound concentration profiles for PBUTs and the effects of dialysate flow rate and dialyzer size on PBUT removal. Model simulations suggest that an increase in dialysate flow rate improves the reduction ratio (and removal) of strongly protein-bound toxins, namely, indoxyl sulfate and p-cresyl sulfate, while for weakly bound toxins, namely, indole-3-acetic acid and p-cresyl glucuronide, an increase in blood flow rate is advantageous. With improved dialyzer performance, removal of strongly bound PBUTs improves gradually, but marginally. The proposed model can be used for optimizing the dialysis regimen and for in silico testing of novel approaches to enhance removal of PBUTs.

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Section: Introductionmentioning

confidence: 99%

A novel mathematical model of protein-bound uremic toxin kinetics during hemodialysis

Maheshwari

Thijssen

Fuertinger

et al. 2017

Sci Rep

Self Cite

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“…Indeed, de Loor et al observed that when sodium octanoate (a medium chain fatty acid characterized as a binding competitor) was added to normal and uremic serum, p‐CS, and IS were inhibited to bind HSA. Moreover, Tao et al revealed that 0.6 μmol/min of DHA increased IS removal by 25% in an in vitro HD model. The authors therefore argued that protein‐binding competitors may be a new strategy to improve the removal of uremic toxins with HD therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, dialysis techniques have been investigated to improve the quality of life of HD patients, and the current focus has been on ways to increase the clearance rate of protein‐bound uremic toxins. Thus far, new techniques based on a longer time for HD, a higher dialysate flow rate and other factors have increased the clearance rate by no more than 1.5 times that of traditional HD, which has a plasma removal rate of IS and p‐CS of approximately 7% …”

Section: Discussionmentioning

confidence: 99%

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A possible link between polyunsaturated fatty acids and uremic toxins from the gut microbiota in hemodialysis patients: A hypothesis

Kemp

Esgalhado

Macedo

et al. 2019

Hemodialysis International

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Introduction: Indoxyl sulfate (IS) and p‐cresyl sulfate (p‐CS) are albumin‐bound uremic toxins that are difficult to remove by hemodialysis (HD). Human serum albumin (HSA) carries several compounds, including fatty acids that can bind to site II of HSA and represent competing ligands for uremic toxins. The aim of this study was to investigate the association between fatty acids and uremic toxin plasma levels in patients undergoing HD. Methods: Thirty‐three HD patients (51.5% male, 54.9 ± 10.2 years old, 44.63 ± 28.4 months on HD, albumin level of 3.8 ± 0.3 g/dL) were evaluated. The erythrocyte fatty acid content (saturated fatty acid [SFA], monounsaturated fatty acid [MUFA], and polyunsaturated fatty acid [PUFA]) was measured by gas chromatography, and total IS and p‐CS plasma levels were measured by reversed‐phase high‐performance liquid chromatography. Findings: The mean percentages of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) + DHA and gamma‐linolenic (GLA) acid in the erythrocyte membrane were 1.35% ± 0.74%, 1.85% ± 0.79%, and 0.33% ± 0.26%, respectively. The mean levels of IS and p‐CS were 19.4 ± 11.9 mg/dL and 101.5 ± 57.2 mg/dL, respectively. There was no significant association between SFA and MUFA and IS and p‐CS; however, a negative correlation was found between p‐CS and specific PUFAs, and the association between GLA and p‐CS levels was retained after adjusting for potential confounding variables (β = −0.49, P = 0.007). Discussion: Polyunsaturated fatty acids may contribute to the decrease in p‐CS uremic toxin plasma levels in patients with chronic kidney disease undergoing HD.

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“…Another area of research concerns altering the dialysis milieu in order to affect the binding of URS to plasma proteins. Examples of this effort which have data supporting their use include using hypertonic solution, the use of albumin-binding site competitors such as tryptophan and docosahexaenoic acid, increasing temperature, plasma dilutions, and pH manipulation of the dialysate [47,[90][91][92][93][94].…”

Section: Dialysismentioning

confidence: 99%

Uremic Retention Solutes

Ackley¹,

Soiefer²,

Etinger³

et al. 2018

Aspects in Dialysis

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This chapter will address the broad subject of uremic retention solutes (URS), also known as uremic toxins. Some of these solutes had been recognized for decades, and in 1999 when the European Uremic Toxin Work Group was established, a fuller description of URS was presented. The group sought to identify and characterize the solutes in the serum of patients with impaired glomerular filtration, in order to explore their role in the pathogenesis of the uremic syndrome and improve current therapeutic options. This chapter will review the different types of URS, as well as the adverse effects associated with their accumulation. It will also cover current and potential therapeutic approaches to reduce their levels.

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Enhanced Indoxyl Sulfate Dialyzer Clearance with the Use of Binding Competitors

Cited by 26 publications

References 51 publications

A novel mathematical model of protein-bound uremic toxin kinetics during hemodialysis

A novel mathematical model of protein-bound uremic toxin kinetics during hemodialysis

A possible link between polyunsaturated fatty acids and uremic toxins from the gut microbiota in hemodialysis patients: A hypothesis

Uremic Retention Solutes

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