Protein-Bound Uremic Toxin Profiling as a Tool to Optimize Hemodialysis

PLoS One. 2016 Jan 22;11(1):e0147159. doi: 10.1371/journal.pone.0147159. eCollection 2016.


Aim: We studied various hemodialysis strategies for the removal of protein-bound solutes, which are associated with cardiovascular damage.

Methods: This study included 10 patients on standard (3 x 4 h/week) high-flux hemodialysis. Blood was collected at the dialyzer inlet and outlet at several time points during a midweek session. Total and free concentration of several protein-bound solutes was determined as well as urea concentration. Per solute, a two-compartment kinetic model was fitted to the measured concentrations, estimating plasmatic volume (V1), total distribution volume (V tot) and intercompartment clearance (K21). This calibrated model was then used to calculate which hemodialysis strategy offers optimal removal. Our own in vivo data, with the strategy variables entered into the mathematical simulations, was then validated against independent data from two other clinical studies.

Results: Dialyzer clearance K, V1 and V tot correlated inversely with percentage of protein binding. All Ks were different from each other. Of all protein-bound solutes, K21 was 2.7-5.3 times lower than that of urea. Longer and/or more frequent dialysis that processed the same amount of blood per week as standard 3 x 4 h dialysis at 300 mL/min blood flow showed no difference in removal of strongly bound solutes. However, longer and/or more frequent dialysis strategies that processed more blood per week than standard dialysis were markedly more adequate. These conclusions were successfully validated.

Conclusion: When blood and dialysate flow per unit of time and type of hemodialyzer are kept the same, increasing the amount of processed blood per week by increasing frequency and/or duration of the sessions distinctly increases removal.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Humans
  • Kinetics
  • Models, Biological
  • Protein Binding
  • Proteins / metabolism*
  • Renal Dialysis*
  • Toxins, Biological / metabolism*
  • Uremia / metabolism*


  • Proteins
  • Toxins, Biological

Grant support

This study was supported by FWO Vlaanderen - G0A4614N. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.