title: Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of Chronic Kidney Disease and during Hemodialysis.
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 (CT) 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/CT 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.
authors.affiliation: Department of Internal Medicine, Nephrology Section, Ghent University Hospital, Ghent 9000, Belgium. olivier.deltombe@ugent.be.
authors.forename: Olivier
authors.initials: O
authors.lastname: Deltombe
authors.affiliation: Department of Internal Medicine, Nephrology Section, Ghent University Hospital, Ghent 9000, Belgium. wim.vanbiesen@ugent.be.
authors.forename: Wim
authors.initials: W
authors.lastname: Van Biesen
authors.affiliation: Department of Internal Medicine, Nephrology Section, Ghent University Hospital, Ghent 9000, Belgium. griet.glorieux@ugent.be.
authors.forename: Griet
authors.initials: G
authors.lastname: Glorieux
authors.affiliation: Division of Nephrology, Amiens University Hospital, Amiens 80000, France. massy@u-picardie.fr.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Massy
authors.affiliation: Department of Internal Medicine, Nephrology Section, Ghent University Hospital, Ghent 9000, Belgium. annemie.dhondt@ugent.be.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Dhondt
authors.affiliation: Department of Internal Medicine, Nephrology Section, Ghent University Hospital, Ghent 9000, Belgium. sunny.eloot@ugent.be.
authors.forename: Sunny
authors.initials: S
authors.lastname: Eloot
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003408:Cresols / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D020719:Glucuronides / Q000097:blood; D006626:Hippurates / Q000097:blood; D006801:Humans; D007200:Indican / Q000097:blood; D007210:Indoleacetic Acids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000628:therapy; D012709:Serum Albumin / Q000378:metabolism; D012720:Severity of Illness Index; D013463:Sulfuric Acid Esters / Q000097:blood; D014511:Uremia / Q000097:blood* / Q000628:therapy
chemical_list: C485699:4-cresylglucuronide; D003408:Cresols; D020719:Glucuronides; D006626:Hippurates; D007210:Indoleacetic Acids; D012709:Serum Albumin; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; C030737:indoleacetic acid; D007200:Indican; C030514:hippuric acid
keywords: chronic kidney disease; hemodialysis; hippuric acid; indole-3-acetic acid; indoxyl sulfate; p-cresylglucuronide; p-cresylsulfate; protein binding; uremic toxins