Predicting the Impact of Polysulfone Dialyzers and Binder Dialysate Flow Rate on Bilirubin Removal

Overview

Journal Bioengineering (Basel)

Date 2025 Jan 8

PMID 39768080

Authors

Alexander Novokhodko

Nanye Du

Shaohang Hao

Ziyuan Wang

Zhiquan Shu

Suhail Ahmad

Dayong Gao

Affiliations

Soon will be listed here.

Abstract

Liver failure is the 12th leading cause of death worldwide. Protein-bound toxins such as bilirubin are responsible for many complications of the disease. Binder dialysis systems use albumin or another binding molecule in dialysate and detoxifying sorbent columns to remove these toxins. Systems like the molecular adsorbent recirculating system and BioLogic-DT have existed since the 1990s, but survival benefits in randomized controlled trials have not been consistent. New binder dialysis systems, including open albumin dialysis and the Advanced Multi-Organ Replacement system, are being developed. Optimal conditions for binder dialysis have not been established. We developed and validated a computational model of bound solute dialysis. It predicted the impact of changing between two test setups using different polysulfone dialyzers (F3 and F6HPS). We then predicted the impact of varying the dialysate flow rate on toxin removal. We found that bilirubin removal declines with dialysate flow rate. This can be explained through a linear decline in free bilirubin membrane permeability. Our model quantifies this decline through a single parameter (polysulfone dialyzers). Validation for additional dialyzers and flow rates will be needed. This model will benefit clinical trials by predicting optimal dialyzer and flow rate conditions. Accounting for toxin adsorption onto the dialyzer membrane may improve results further.

References

Leypoldt J, Cheung A, Agodoa L, Daugirdas J, Greene T, Keshaviah P . Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates. The Hemodialysis (HEMO) Study. Kidney Int. 1997; 51(6):2013-7. DOI: 10.1038/ki.1997.274. View

Patzer 2nd J, Safta S, Miller R . Slow continuous ultrafiltration with bound solute dialysis. ASAIO J. 2006; 52(1):47-58. DOI: 10.1097/01.mat.0000196524.36394.0d. View

Weisiger R, Ostrow J, Koehler R, Webster C, MUKERJEE P, Pascolo L . Affinity of human serum albumin for bilirubin varies with albumin concentration and buffer composition: results of a novel ultrafiltration method. J Biol Chem. 2001; 276(32):29953-60. DOI: 10.1074/jbc.M104628200. View

Rubaltelli F, Jori G . Visible light irradiation of human and bovine serum albumin-bilirubin complex. Photochem Photobiol. 1979; 29(5):991-1000. DOI: 10.1111/j.1751-1097.1979.tb07803.x. View

Depner T, Greene T, Daugirdas J, Cheung A, Gotch F, Leypoldt J . Dialyzer performance in the HEMO Study: in vivo K0A and true blood flow determined from a model of cross-dialyzer urea extraction. ASAIO J. 2004; 50(1):85-93. DOI: 10.1097/01.mat.0000104824.55517.6c. View

Villarroel F, Klein E, Holland F . Solute flux in hemodialysis and hemofiltration membranes. Trans Am Soc Artif Intern Organs. 1977; 23:225-33. DOI: 10.1097/00002480-197700230-00061. View

Faerch T, Jacobsen J . Determination of association and dissociation rate constants for bilirubin--bovine serum albumin. Arch Biochem Biophys. 1975; 168(2):351-7. DOI: 10.1016/0003-9861(75)90263-5. View

MacCoun R, Perlmutter S . Blind analysis: Hide results to seek the truth. Nature. 2015; 526(7572):187-9. DOI: 10.1038/526187a. View

Patzer 2nd J, Bane S . Bound solute dialysis. ASAIO J. 2003; 49(3):271-81. DOI: 10.1097/01.mat.0000065378.73558.83. View

10.

MICHAELS A . Operating parameters and performance criteria for hemodialyzers and other membrane-separation devices. Trans Am Soc Artif Intern Organs. 1966; 12:387-92. View

11.

Eloot S, De Vos J, de Vos F, Hombrouckx R, Verdonck P . Middle molecule removal in low-flux polysulfone dialyzers: impact of flows and surface area on whole-body and dialyzer clearances. Hemodial Int. 2005; 9(4):399-408. DOI: 10.1111/j.1492-7535.2005.01159.x. View

12.

Peng Z, Yang Y, Luo J, Nie C, Ma L, Cheng C . Nanofibrous polymeric beads from aramid fibers for efficient bilirubin removal. Biomater Sci. 2016; 4(9):1392-401. DOI: 10.1039/c6bm00328a. View

13.

Saliba F, Camus C, Durand F, Mathurin P, Letierce A, Delafosse B . Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial. Ann Intern Med. 2013; 159(8):522-31. DOI: 10.7326/0003-4819-159-8-201310150-00005. View

14.

Meyer T, Peattie J, Miller J, Dinh D, Recht N, Walther J . Increasing the clearance of protein-bound solutes by addition of a sorbent to the dialysate. J Am Soc Nephrol. 2007; 18(3):868-74. DOI: 10.1681/ASN.2006080863. View

15.

Rahelic D, Kujundzic M, Romic Z, Brkic K, Petrovecki M . Serum concentration of zinc, copper, manganese and magnesium in patients with liver cirrhosis. Coll Antropol. 2006; 30(3):523-8. View

16.

. Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024; 403(10440):2100-2132. PMC: 11126520. DOI: 10.1016/S0140-6736(24)00367-2. View

17.

Varchanis S, Dimakopoulos Y, Wagner C, Tsamopoulos J . How viscoelastic is human blood plasma?. Soft Matter. 2018; 14(21):4238-4251. DOI: 10.1039/C8SM00061A. View

18.

Jacobsen J . Studies of the affinity of human serum albumin for binding of bilirubin at different temperatures and ionic strength. Int J Pept Protein Res. 1977; 9(3):235-9. DOI: 10.1111/j.1399-3011.1977.tb03486.x. View

19.

Patzer J . Principles of bound solute dialysis. Ther Apher Dial. 2006; 10(2):118-24. DOI: 10.1111/j.1744-9987.2006.00352.x. View

20.

Lakovic K, Ai J, DAbbondanza J, Tariq A, Sabri M, Alarfaj A . Bilirubin and its oxidation products damage brain white matter. J Cereb Blood Flow Metab. 2014; 34(11):1837-47. PMC: 4269762. DOI: 10.1038/jcbfm.2014.154. View