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Exploring binding characteristics and the related competition of different protein-bound uremic toxins.
Biochimie. 2017 Aug; 139:20-26.B

Abstract

Little is known about potential differences in binding characteristics of protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD) versus healthy controls. The question arises whether eventual differences are attributed to (i) the elevated levels of competing uremic toxins, and/or (ii) post-translational modifications of albumin. We evaluated the binding characteristics of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (pCS) by deriving a binding curve in three distinct conditions: (i) serum from healthy controls (healthy serum), (ii) blank serum from hemodialysis patients (blank HD serum; i.e. cleared from uremic toxins), and (iii) non-treated serum from HD patients (HD serum). Additionally, the mutual binding competition of these uremic toxins was studied in blank HD in pairs. In both experiments, equilibrium dialysis (37 °C, 5 h) was used to separate the free and bound fractions of each PBUT. Free and total PBUT concentrations were quantified by an ultra-high performance liquid chromatography method with tandem mass spectrometer detection and the percentage protein binding (%PB) of each PBUT was calculated. For all four compounds, the binding capacity of healthy serum was higher than blank HD serum, which was comparable to non-treated HD serum, except for HA. The competition experiments revealed that at high uremic concentrations, mutual competition was observed for the strongly bound PBUTs IS and pCS. The %PB of the weakly bound HA and IAA was lower (trend) only for the addition to blank HD serum containing the strongly bound IS or pCS. There is an intrinsic impact on protein binding in uremia, revealing a lower binding capacity, as compared to healthy controls. Competitive binding is only relevant for the strongly bound PBUTs at high uremic concentrations. In addition, at least part of the effect on binding capacity can be attributed to post-translational modifications of albumin.

Authors+Show Affiliations

Renal Division - Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. Electronic address: Olivier.Deltombe@UGent.be.Department of Nephrology - University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. Electronic address: jetty.deloor@uzleuven.be.Renal Division - Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. Electronic address: Griet.Glorieux@UGent.be.Renal Division - Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. Electronic address: Annemie.Dhondt@UGent.be.Renal Division - Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. Electronic address: Wim.VanBiesen@UGent.be.Department of Nephrology - University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. Electronic address: bjorn.meijers@uzleuven.be.Renal Division - Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. Electronic address: Sunny.Eloot@UGent.be.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

28528271

Citation

Deltombe, Olivier, et al. "Exploring Binding Characteristics and the Related Competition of Different Protein-bound Uremic Toxins." Biochimie, vol. 139, 2017, pp. 20-26.
Deltombe O, de Loor H, Glorieux G, et al. Exploring binding characteristics and the related competition of different protein-bound uremic toxins. Biochimie. 2017;139:20-26.
Deltombe, O., de Loor, H., Glorieux, G., Dhondt, A., Van Biesen, W., Meijers, B., & Eloot, S. (2017). Exploring binding characteristics and the related competition of different protein-bound uremic toxins. Biochimie, 139, 20-26. https://doi.org/10.1016/j.biochi.2017.05.010
Deltombe O, et al. Exploring Binding Characteristics and the Related Competition of Different Protein-bound Uremic Toxins. Biochimie. 2017;139:20-26. PubMed PMID: 28528271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exploring binding characteristics and the related competition of different protein-bound uremic toxins. AU - Deltombe,Olivier, AU - de Loor,Henriette, AU - Glorieux,Griet, AU - Dhondt,Annemieke, AU - Van Biesen,Wim, AU - Meijers,Björn, AU - Eloot,Sunny, Y1 - 2017/05/17/ PY - 2017/03/22/received PY - 2017/05/16/accepted PY - 2017/5/22/pubmed PY - 2017/9/13/medline PY - 2017/5/22/entrez KW - Chronic kidney disease KW - Hippuric acid KW - Indole-3-acetic acid KW - Indoxyl sulfate KW - Uremic toxin KW - p-cresylsulfate SP - 20 EP - 26 JF - Biochimie JO - Biochimie VL - 139 N2 - Little is known about potential differences in binding characteristics of protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD) versus healthy controls. The question arises whether eventual differences are attributed to (i) the elevated levels of competing uremic toxins, and/or (ii) post-translational modifications of albumin. We evaluated the binding characteristics of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (pCS) by deriving a binding curve in three distinct conditions: (i) serum from healthy controls (healthy serum), (ii) blank serum from hemodialysis patients (blank HD serum; i.e. cleared from uremic toxins), and (iii) non-treated serum from HD patients (HD serum). Additionally, the mutual binding competition of these uremic toxins was studied in blank HD in pairs. In both experiments, equilibrium dialysis (37 °C, 5 h) was used to separate the free and bound fractions of each PBUT. Free and total PBUT concentrations were quantified by an ultra-high performance liquid chromatography method with tandem mass spectrometer detection and the percentage protein binding (%PB) of each PBUT was calculated. For all four compounds, the binding capacity of healthy serum was higher than blank HD serum, which was comparable to non-treated HD serum, except for HA. The competition experiments revealed that at high uremic concentrations, mutual competition was observed for the strongly bound PBUTs IS and pCS. The %PB of the weakly bound HA and IAA was lower (trend) only for the addition to blank HD serum containing the strongly bound IS or pCS. There is an intrinsic impact on protein binding in uremia, revealing a lower binding capacity, as compared to healthy controls. Competitive binding is only relevant for the strongly bound PBUTs at high uremic concentrations. In addition, at least part of the effect on binding capacity can be attributed to post-translational modifications of albumin. SN - 1638-6183 UR - https://www.unboundmedicine.com/medline/citation/28528271/Exploring_binding_characteristics_and_the_related_competition_of_different_protein_bound_uremic_toxins_ DB - PRIME DP - Unbound Medicine ER -