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

A kinetic model based on first principles, for beta(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 +/- A 0.75 L, plasma fraction in extracellular compartment (f (P)) of 0.39 +/- A 0.03, and inter-compartmental clearance of 44 +/- A 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 beta(2)-microglobulin, and also lead to quantitative inclusion of intra-dialytic exercise in the future.