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.
Highlights
Uremic syndrome is characterized by the retention of a large number of compounds, which in healthy persons are excreted by the kidneys
To unravel changes in protein binding in the hemodialyzer, as well as during the course of a hemodialysis session, data were taken from a second cross-sectional study including 10 stable HD patients
We explored the protein binding of uremic toxins in patients with different stages of chronic kidney disease (CKD) and during a hemodialysis session
Summary
Uremic syndrome is characterized by the retention of a large number of compounds, which in healthy persons are excreted by the kidneys Some of those retention solutes interact negatively with biological functions and are called uremic toxins. These toxins are classified into three groups: the free small water-soluble solutes (molecular weight (MW) < 500 Da), the middle molecules (MW > 500 Da) and the protein-bound solutes [1,2]. The latter solutes have a protein binding ranging from around 10% (e.g., p-cresylglucuronide) to near 100% (e.g., p-cresylsulfate). This information might be useful in the development of new removal strategies aiming at the optimization of dialysis
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