Sensitivity analysis for estimating urea kinetics parameters during hemodialysis

In this paper a time-varying volume, double-pool urea kinetics model is considered and a sensitivity analysis is carried out to determine those patient parameters that have greater influence on the time course of blood urea nitrogen concentration (BUN) during and between dialysis treatment. The model parameters include the urea generation rate, the initial distribution volume of the urea, the ratio between intracellular and extracellular volumes, and the mass transfer coefficient between the two pools. The analysis demonstrates that BUN is highly sensitive to the urea generation rate and total distribution volume whereas it is influenced by the remaining parameters to a much lesser extent. In addition, the location of the absolute maxima of BUN sensitivity functions suggests the rational placement of a reduced number of blood samples that may still allow sufficiently accurate estimates for the parameters of clinical interest, such as the urea generation rate, total distribution volume, and the ratio between intracellular and extracellular volumes. This conclusion has been confirmed by simulation studies where parameter estimation has been performed with a varying number of observation points.