Transport and reaction phenomena in multilayer membranes functioning as bioartificial kidney devices

R. Refoyo, E. D. Skouras, N. V. Chevtchik, D. Stamatialis, V. N. Burganos (Corresponding Author)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Classic hemodialysis only provides a limited removal of protein bound uremic toxins (PBUT) in patients with chronic kidney disease. A bioartificial kidney device, BAK, composed of a living cell monolayer of conditionally immortalized proximal tubule epithelial kidney cells (ciPTEC) cultured of hollow fiber polymeric membrane can remove protein bound uremic toxins from the blood in combination with classic hemodialysis. The development and clinical implementation of the BAK requires lots of optimization. This investigation is expensive and time consuming therefore modeling studies could help to optimize experiments and improve its design. In this work, a 3D mathematical model of the BAK is developed. The transport and reaction mechanisms associated with the removal of PBUT indoxyl sulfate are considered and various conditions are simulated. The model describes a single hollow fiber membrane and considers different domains for the blood flow, the membrane, the cell monolayer, and the dialysate region. A mathematical description of the relevant transport and/or reaction mechanisms is provided in each domain, and the corresponding differential equations are solved numerically. Since not all the modeling constants are experimentally available, a parametric study is performed for their quantification, including the active transport kinetics of the toxins through the cell monolayer, in comparison to the passive transport rates by diffusion. The parametric study also provides a background for the extraction of usually unknown quantities, including notably the Organic Anion Transporter (OAT) concentrations, with the support of experimental data. Satisfactory reproduction of experimental findings is achieved, and the role of systemic variables that affect significantly the uremic toxin removal is identified.

Original languageEnglish
Pages (from-to)61-71
Number of pages11
JournalJournal of membrane science
Volume565
Early online date7 Aug 2018
DOIs
Publication statusPublished - 1 Nov 2018

Fingerprint

kidneys
Monolayers
Multilayers
membranes
proteins
Proteins
Membranes
Kidney
Equipment and Supplies
Renal Dialysis
hollow
Blood
kidney diseases
Indican
Organic Anion Transporters
transporter
Polymeric membranes
Proximal Kidney Tubule
fibers
Fibers

Keywords

  • Bioartificial kidney device
  • Cell monolayer modeling
  • Hollow fiber membrane
  • Organic ion transporters
  • Protein-bound uremic toxins

Cite this

Refoyo, R. ; Skouras, E. D. ; Chevtchik, N. V. ; Stamatialis, D. ; Burganos, V. N. / Transport and reaction phenomena in multilayer membranes functioning as bioartificial kidney devices. In: Journal of membrane science. 2018 ; Vol. 565. pp. 61-71.
@article{4224429775a748e6bf681e83bbf795db,
title = "Transport and reaction phenomena in multilayer membranes functioning as bioartificial kidney devices",
abstract = "Classic hemodialysis only provides a limited removal of protein bound uremic toxins (PBUT) in patients with chronic kidney disease. A bioartificial kidney device, BAK, composed of a living cell monolayer of conditionally immortalized proximal tubule epithelial kidney cells (ciPTEC) cultured of hollow fiber polymeric membrane can remove protein bound uremic toxins from the blood in combination with classic hemodialysis. The development and clinical implementation of the BAK requires lots of optimization. This investigation is expensive and time consuming therefore modeling studies could help to optimize experiments and improve its design. In this work, a 3D mathematical model of the BAK is developed. The transport and reaction mechanisms associated with the removal of PBUT indoxyl sulfate are considered and various conditions are simulated. The model describes a single hollow fiber membrane and considers different domains for the blood flow, the membrane, the cell monolayer, and the dialysate region. A mathematical description of the relevant transport and/or reaction mechanisms is provided in each domain, and the corresponding differential equations are solved numerically. Since not all the modeling constants are experimentally available, a parametric study is performed for their quantification, including the active transport kinetics of the toxins through the cell monolayer, in comparison to the passive transport rates by diffusion. The parametric study also provides a background for the extraction of usually unknown quantities, including notably the Organic Anion Transporter (OAT) concentrations, with the support of experimental data. Satisfactory reproduction of experimental findings is achieved, and the role of systemic variables that affect significantly the uremic toxin removal is identified.",
keywords = "Bioartificial kidney device, Cell monolayer modeling, Hollow fiber membrane, Organic ion transporters, Protein-bound uremic toxins",
author = "R. Refoyo and Skouras, {E. D.} and Chevtchik, {N. V.} and D. Stamatialis and Burganos, {V. N.}",
year = "2018",
month = "11",
day = "1",
doi = "10.1016/j.memsci.2018.08.007",
language = "English",
volume = "565",
pages = "61--71",
journal = "Journal of membrane science",
issn = "0376-7388",
publisher = "Elsevier",

}

Transport and reaction phenomena in multilayer membranes functioning as bioartificial kidney devices. / Refoyo, R.; Skouras, E. D.; Chevtchik, N. V.; Stamatialis, D.; Burganos, V. N. (Corresponding Author).

In: Journal of membrane science, Vol. 565, 01.11.2018, p. 61-71.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Transport and reaction phenomena in multilayer membranes functioning as bioartificial kidney devices

AU - Refoyo, R.

AU - Skouras, E. D.

AU - Chevtchik, N. V.

AU - Stamatialis, D.

AU - Burganos, V. N.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Classic hemodialysis only provides a limited removal of protein bound uremic toxins (PBUT) in patients with chronic kidney disease. A bioartificial kidney device, BAK, composed of a living cell monolayer of conditionally immortalized proximal tubule epithelial kidney cells (ciPTEC) cultured of hollow fiber polymeric membrane can remove protein bound uremic toxins from the blood in combination with classic hemodialysis. The development and clinical implementation of the BAK requires lots of optimization. This investigation is expensive and time consuming therefore modeling studies could help to optimize experiments and improve its design. In this work, a 3D mathematical model of the BAK is developed. The transport and reaction mechanisms associated with the removal of PBUT indoxyl sulfate are considered and various conditions are simulated. The model describes a single hollow fiber membrane and considers different domains for the blood flow, the membrane, the cell monolayer, and the dialysate region. A mathematical description of the relevant transport and/or reaction mechanisms is provided in each domain, and the corresponding differential equations are solved numerically. Since not all the modeling constants are experimentally available, a parametric study is performed for their quantification, including the active transport kinetics of the toxins through the cell monolayer, in comparison to the passive transport rates by diffusion. The parametric study also provides a background for the extraction of usually unknown quantities, including notably the Organic Anion Transporter (OAT) concentrations, with the support of experimental data. Satisfactory reproduction of experimental findings is achieved, and the role of systemic variables that affect significantly the uremic toxin removal is identified.

AB - Classic hemodialysis only provides a limited removal of protein bound uremic toxins (PBUT) in patients with chronic kidney disease. A bioartificial kidney device, BAK, composed of a living cell monolayer of conditionally immortalized proximal tubule epithelial kidney cells (ciPTEC) cultured of hollow fiber polymeric membrane can remove protein bound uremic toxins from the blood in combination with classic hemodialysis. The development and clinical implementation of the BAK requires lots of optimization. This investigation is expensive and time consuming therefore modeling studies could help to optimize experiments and improve its design. In this work, a 3D mathematical model of the BAK is developed. The transport and reaction mechanisms associated with the removal of PBUT indoxyl sulfate are considered and various conditions are simulated. The model describes a single hollow fiber membrane and considers different domains for the blood flow, the membrane, the cell monolayer, and the dialysate region. A mathematical description of the relevant transport and/or reaction mechanisms is provided in each domain, and the corresponding differential equations are solved numerically. Since not all the modeling constants are experimentally available, a parametric study is performed for their quantification, including the active transport kinetics of the toxins through the cell monolayer, in comparison to the passive transport rates by diffusion. The parametric study also provides a background for the extraction of usually unknown quantities, including notably the Organic Anion Transporter (OAT) concentrations, with the support of experimental data. Satisfactory reproduction of experimental findings is achieved, and the role of systemic variables that affect significantly the uremic toxin removal is identified.

KW - Bioartificial kidney device

KW - Cell monolayer modeling

KW - Hollow fiber membrane

KW - Organic ion transporters

KW - Protein-bound uremic toxins

UR - http://www.scopus.com/inward/record.url?scp=85051643700&partnerID=8YFLogxK

U2 - 10.1016/j.memsci.2018.08.007

DO - 10.1016/j.memsci.2018.08.007

M3 - Article

VL - 565

SP - 61

EP - 71

JO - Journal of membrane science

JF - Journal of membrane science

SN - 0376-7388

ER -