A novel mathematical model of protein-bound uremic toxin kinetics during hemodialysis
Vaibhav Maheshwari, Stephan Thijssen, Xia Tao, Doris Fuertinger, Franz Kappel, Peter Kotanko
Source record
Source: Crossref
Published: Sep 4, 2017
DOI: 10.1038/s41598-017-10981-z
Open original source ↗Source abstract
Abstract Protein-bound uremic toxins (PBUTs) are difficult to remove by conventional hemodialysis; a high degree of protein binding reduces the free fraction of toxins and decreases their diffusion across dialyzer membranes. Mechanistic understanding of PBUT kinetics can open new avenues to improve their dialytic removal. We developed a comprehensive model of PBUT kinetics that comprises: (1) a three-compartment patient model, (2) a dialyzer model. The model accounts for dynamic equilibrium between protein, toxin, and the protein-toxin complex. Calibrated and validated using clinical and experimental data from the literature, the model predicts key aspects of PBUT kinetics, including the free and bound concentration profiles for PBUTs and the effects of dialysate flow rate and dialyzer size on PBUT removal. Model simulations suggest that an increase in dialysate flow rate improves the reduction ratio (and removal) of strongly protein-bound toxins, namely, indoxyl sulfate and p-cresyl sulfate, while for weakly bound toxins, namely, indole-3-acetic acid and p-cresyl glucuronide, an increase in blood flow rate is advantageous. With improved dialyzer performance, removal of strongly bound PBUTs improves gradually, but marginally. The proposed model can be used for optimizing the dialysis regimen and for in silico testing of novel approaches to enhance removal of PBUTs.
Evidence graph
No public relationships recorded yet.
Integrity note: This page is a factual metadata record created by deterministic ingestion. It is not a claim that the work moves a mathematical frontier or has been independently verified.