A Regional Blood Flow Model for β2-Microglobulin Kinetics and for Simulating Intra-dialytic Exercise Effect

• Published in: Annals of biomedical engineering Vol. 39; no. 12; pp. 2879 - 2890
• Main Authors: Maheshwari, Vaibhav, Samavedham, Lakshminarayanan, Rangaiah, Gade P.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2011
• Subjects: beta 2-Microglobulin - metabolism; Biochemistry; Biological and Medical Physics; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Biophysics; Blood Circulation - physiology; Classical Mechanics; Computer Simulation; Exercise - physiology; Female; Humans; Male; Models, Biological; Renal Dialysis; Inter-compartmental clearance; Hemodiafiltration; Kinetic modeling; Plasma fraction; identifiability analysis; Cardiac output; Toxin distribution volume
• ISSN: 0090-6964; 1573-9686; 1573-9686
• DOI: 10.1007/s10439-011-0383-5

A kinetic model based on first principles, for β 2 -microglobulin, is presented to obtain precise parameter estimates for individual patient. To reduce the model complexity, the number of model parameters was reduced using a priori identifiability analysis. The model validity was confirmed with the clinical data of ten renal patients on post-dilution hemodiafiltration. The model fit resulted in toxin distribution volume ( V d ) of 14.22 ± 0.75 L, plasma fraction in extracellular compartment ( f P ) of 0.39 ± 0.03, and inter-compartmental clearance of 44 ± 4.1 mL min −1 . Parameter estimates suggest that V d and f P are much higher in hemodialysis patients than in normal subjects. The developed model predicts larger removed toxin mass than that predicted by the two-pool model. On the application front, the developed model was employed to explain the effect of intra-dialytic exercise on toxin removal. The presented simulations suggest that intra-dialytic exercise not only increases the blood flow to low flow region, but also decreases the inter-compartmental resistance. Combined, they lead to increased toxin removal during dialysis and reduced post-dialysis rebound. The developed model can assist in suggesting the improved dialysis dose based on β 2 -microglobulin, and also lead to quantitative inclusion of intra-dialytic exercise in the future.