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

Maheshwari, Vaibhav; Thijssen, Stephan; Kotanko, Peter

doi:10.3390/toxins13090622

Cited by 24 publications

(20 citation statements)

References 28 publications

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“…While we are unable to explore the underlying mechanisms, there are hypotheses for these changes. Tryptophan is heavily protein bound and before hemodialysis there is competition of uremic toxins and tryptophan for binding spots on plasma proteins such as albumin [ 32 ]. During hemodialysis, removal of uremic toxins frees up binding spots and may lead to an extravascular to intravascular shift of tryptophan.…”

Section: Discussionmentioning

confidence: 99%

Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients

et al. 2022

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Patients dependent on chronic hemodialysis treatment are prone to malnutrition, at least in part due to insufficient nutrient intake, metabolic derangements, and chronic inflammation. Losses of amino acids during hemodialysis may be an important additional contributor. In this study, we assessed changes in plasma amino acid concentrations during hemodialysis, quantified intradialytic amino acid losses, and investigated whether plasma amino acid concentrations and amino acid losses by hemodialysis and urinary excretion are associated with fatigue. The study included a total of 59 hemodialysis patients (65 ± 15 years, 63% male) and 33 healthy kidney donors as controls (54 ± 10 years, 45% male). Total plasma essential amino acid concentration before hemodialysis was lower in hemodialysis patients compared with controls (p = 0.006), while total non-essential amino acid concentration did not differ. Daily amino acid losses were 4.0 ± 1.3 g/24 h for hemodialysis patients and 0.6 ± 0.3 g/24 h for controls. Expressed as proportion of protein intake, daily amino acid losses of hemodialysis patients were 6.7 ± 2.4% of the total protein intake, compared to 0.7 ± 0.3% for controls (p < 0.001). Multivariable regression analyses demonstrated that hemodialysis efficacy (Kt/V) was the primary determinant of amino acid losses (Std. β = 0.51; p < 0.001). In logistic regression analyses, higher plasma proline concentrations were associated with higher odds of severe fatigue (OR (95% CI) per SD increment: 3.0 (1.3; 9.3); p = 0.03), while higher taurine concentrations were associated with lower odds of severe fatigue (OR (95% CI) per log2 increment: 0.3 (0.1; 0.7); p = 0.01). Similarly, higher daily taurine losses were also associated with lower odds of severe fatigue (OR (95% CI) per log2 increment: 0.64 (0.42; 0.93); p = 0.03). Lastly, a higher protein intake was associated with lower odds of severe fatigue (OR (95% CI) per SD increment: 0.2 (0.04; 0.5); p = 0.007). Future studies are warranted to investigate the mechanisms underlying these associations and investigate the potential of taurine supplementation.

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Section: Discussionmentioning

confidence: 99%

Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients

et al. 2022

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“…A promising technique for the removal of PBUTs is binding competition using pharmaceutical drugs as displacers [ 92 , 93 ]. This technique holds out great hopes for future haemodialysis.…”

Section: Strategies Aimed At the Removal Of Utsmentioning

confidence: 99%

“…The IS and PCS removal improved by 135.6% and 272%, respectively [ 95 ]. This study highlights an important point regarding the use of a binding competitor cocktail that targets multiple binding sites on BSA, which leads to higher PBUTs removal rates during dialysis [ 92 ].…”

Section: Strategies Aimed At the Removal Of Utsmentioning

confidence: 99%

Interaction of Human Serum Albumin with Uremic Toxins: The Need of New Strategies Aiming at Uremic Toxins Removal

et al. 2022

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Chronic kidney disease (CKD) is acknowledged worldwide to be a grave threat to public health, with the number of US end-stage kidney disease (ESKD) patients increasing steeply from 10,000 in 1973 to 703,243 in 2015. Protein-bound uremic toxins (PBUTs) are excreted by renal tubular secretion in healthy humans, but hardly removed by traditional haemodialysis (HD) in ESKD patients. The accumulation of these toxins is a major contributor to these sufferers’ morbidity and mortality. As a result, some improvements to dialytic removal have been proposed, each with their own upsides and drawbacks. Longer dialysis sessions and hemodiafiltration, though, have not performed especially well, while larger dialyzers, coupled with a higher dialysate flow, proved to have some efficiency in indoxyl sulfate (IS) clearance, but with reduced impact on patients’ quality of life. More efficient in removing PBUTs was fractionated plasma separation and adsorption, but the risk of occlusive thrombosis was worryingly high. A promising technique for the removal of PBUTs is binding competition, which holds great hopes for future HD. This short review starts by presenting the PBUTs chemistry with emphasis on the chemical interactions with the transport protein, human serum albumin (HSA). Recent membrane-based strategies targeting PBUTs removal are also presented, and their efficiency is discussed.

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“…Hemodialysis (HD) has been the most common method of renal replacement therapy worldwide for patients with end-stage renal disease (ESRD) 22 . However, HD is not very effective in removing uremic toxins with medium molecular weight or those binding to proteins, such as indoxyl sulfate (IS), p-Cresylsulfate (PCS), and indole acetic acid (IAA) 23,24 which are associated with the signaling of the inflammatory response, decreasing erythropoiesis and compromising the growth and differentiation of red blood cells in the bone marrow 25,26 . These UTs also induce reactive oxygen species (ROS) as well as inflammation and exert adverse effects on various organs 27 .…”

mentioning

confidence: 99%

Uremic toxins, inflammation biomarkers and hepcidin in older CKD patients switched from high flux HD to OL-HDF

Fanchini

Morales

Silva

et al. 2022

Preprint

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Anemia is a common complication that is associated with mortality in patients with chronic kidney disease (CKD). Despite the use of erythropoiesis-stimulating agents (ESAs) to correct anemia, some patients are hyporesponsive due to the state of micro-inflammation caused by uremic toxins and hepcidin, a hormone that plays a central role in iron homeostasis. Hemodiafiltration (OL-HDF) has been associated with better clearance of uremic toxins, such as indoxyl sulfate (IS), p-cresyl sulfate (PCS) and indole acetic ascorbic (IAA) than conventional hemodialysis (HD). The aim of the study was to evaluate the effect of OL-HDF treatment on the concentration of IS, PCS, IAA, hepcidin and inflammatory biomarkers in CKD patients. Thirty-one patients (> 65 years old) incident in OL-HDF were followed for 6 months. IS, PCS, IAA, biochemical parameters, hepcidin and inflammatory cytokines were evaluated at baseline and after 6 months. We observed a significant decrease in IS and CRP plasma concentration, an increase in hemoglobin and hematocrit after 6 months of treatment with OL-HDF (p <0.05). This prospective observational study demonstrated that OL-HDF was capable to reduce IS and CRP in older patients. Whether this reduction may have an impact on clinical outcomes must be investigated in a future study.

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

Cited by 24 publications

References 28 publications

Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients

Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients

Interaction of Human Serum Albumin with Uremic Toxins: The Need of New Strategies Aiming at Uremic Toxins Removal

Uremic toxins, inflammation biomarkers and hepcidin in older CKD patients switched from high flux HD to OL-HDF

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