A regional blood flow model for β2-microglobulin kinetics and for simulating intra-dialytic exercise effect.

Abstract

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.