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Exploring protein binding of uremic toxins in patients with different stages of chronic kidney disease and during hemodialysis

Olivier Deltombe (UGent) , Wim Van Biesen (UGent) , Griet Glorieux (UGent) , Ziad Massy, Annemieke Dhondt (UGent) and Sunny Eloot (UGent)
(2015) TOXINS. 7(10). p.3933-3946
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Abstract
As protein binding of uremic toxins is not well understood, neither in chronic kidney disease (CKD) progression, nor during a hemodialysis (HD) session, we studied protein binding in two cross-sectional studies. Ninety-five CKD 2 to 5 patients and ten stable hemodialysis patients were included. Blood samples were taken either during the routine ambulatory visit (CKD patients) or from blood inlet and outlet line during dialysis (HD patients). Total (C-T) and free concentrations were determined of p-cresylglucuronide (pCG), hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS) and p-cresylsulfate (pCS), and their percentage protein binding (%PB) was calculated. In CKD patients, %PB/C-T resulted in a positive correlation (all p < 0.001) with renal function for all five uremic toxins. In HD patients, %PB was increased after 120 min of dialysis for HA and at the dialysis end for the stronger (IAA) and the highly-bound (IS and pCS) solutes. During one passage through the dialyzer at 120 min, %PB was increased for HA (borderline), IAA, IS and pCS. These findings explain why protein-bound solutes are difficult to remove by dialysis: a combination of the fact that (i) only the free fraction can pass the filter and (ii) the equilibrium, as it was pre-dialysis, cannot be restored during the dialysis session, as it is continuously disturbed.
Keywords
uremic toxins, p-cresylglucuronide, protein binding, hemodialysis, chronic kidney disease, SOLUTES, ALBUMIN-BINDING, p-cresylsulfate, P-CRESYL SULFATE, INDOXYL SULFATE, hippuric acid, HEMODIAFILTRATION, CRESYLSULPHATE, SERUM, indole-3-acetic acid, indoxyl sulfate, VANCOMYCIN, RELEVANCE, VARIABILITY

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Chicago
Deltombe, Olivier, Wim Van Biesen, Griet Glorieux, Ziad Massy, Annemieke Dhondt, and Sunny Eloot. 2015. “Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of Chronic Kidney Disease and During Hemodialysis.” Toxins 7 (10): 3933–3946.
APA
Deltombe, O., Van Biesen, W., Glorieux, G., Massy, Z., Dhondt, A., & Eloot, S. (2015). Exploring protein binding of uremic toxins in patients with different stages of chronic kidney disease and during hemodialysis. TOXINS, 7(10), 3933–3946.
Vancouver
1.
Deltombe O, Van Biesen W, Glorieux G, Massy Z, Dhondt A, Eloot S. Exploring protein binding of uremic toxins in patients with different stages of chronic kidney disease and during hemodialysis. TOXINS. 2015;7(10):3933–46.
MLA
Deltombe, Olivier, Wim Van Biesen, Griet Glorieux, et al. “Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of Chronic Kidney Disease and During Hemodialysis.” TOXINS 7.10 (2015): 3933–3946. Print.
@article{7088837,
  abstract     = {As protein binding of uremic toxins is not well understood, neither in chronic kidney disease (CKD) progression, nor during a hemodialysis (HD) session, we studied protein binding in two cross-sectional studies. Ninety-five CKD 2 to 5 patients and ten stable hemodialysis patients were included. Blood samples were taken either during the routine ambulatory visit (CKD patients) or from blood inlet and outlet line during dialysis (HD patients). Total (C-T) and free concentrations were determined of p-cresylglucuronide (pCG), hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS) and p-cresylsulfate (pCS), and their percentage protein binding (\%PB) was calculated. In CKD patients, \%PB/C-T resulted in a positive correlation (all p {\textlangle} 0.001) with renal function for all five uremic toxins. In HD patients, \%PB was increased after 120 min of dialysis for HA and at the dialysis end for the stronger (IAA) and the highly-bound (IS and pCS) solutes. During one passage through the dialyzer at 120 min, \%PB was increased for HA (borderline), IAA, IS and pCS. These findings explain why protein-bound solutes are difficult to remove by dialysis: a combination of the fact that (i) only the free fraction can pass the filter and (ii) the equilibrium, as it was pre-dialysis, cannot be restored during the dialysis session, as it is continuously disturbed.},
  author       = {Deltombe, Olivier and Van Biesen, Wim and Glorieux, Griet and Massy, Ziad and Dhondt, Annemieke and Eloot, Sunny},
  issn         = {2072-6651},
  journal      = {TOXINS},
  keyword      = {uremic toxins,p-cresylglucuronide,protein binding,hemodialysis,chronic kidney disease,SOLUTES,ALBUMIN-BINDING,p-cresylsulfate,P-CRESYL SULFATE,INDOXYL SULFATE,hippuric acid,HEMODIAFILTRATION,CRESYLSULPHATE,SERUM,indole-3-acetic acid,indoxyl sulfate,VANCOMYCIN,RELEVANCE,VARIABILITY},
  language     = {eng},
  number       = {10},
  pages        = {3933--3946},
  title        = {Exploring protein binding of uremic toxins in patients with different stages of chronic kidney disease and during hemodialysis},
  url          = {http://dx.doi.org/10.3390/toxins7103933},
  volume       = {7},
  year         = {2015},
}

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