Solute disequilibrium and multicompartment modeling

Mathematical models that simulate the exchange of solute between multiple body compartments have been used to study the distribution, elimination, and transport of urea, water, electrolytes, and other substances in the dialysis patient. Within a compartment, such substances are assumed to be uniformly distributed while exchange between compartments or with the environment may occur in a number of different ways. Diffusion in response to concentration gradients between, for example, intracellular and extracellular spaces, and convection due to blood flow have been identified as the most important transport mechanisms. Any system with more than one compartment may develop nonuniform solute distribution or solute disequilibrium between compartments. The minimum number of compartments required to model a kinetic process such as urea removal during hemodialysis depends on the accuracy and temporal resolution required, with higher resolution calling for more compartments. A two-compartment model is adequate for most clinical purposes. The physiological meaning or anatomic counterparts of the mathematical compartments remain uncertain as both flow and diffusion transport mechanisms contribute to the disequilibrium. Processes such as access and cardiopulmonary recirculation may be represented as additional compartments with small distribution volumes and high mass transport rates. Failure to recognize the effect of multiple compartments will result in an inaccurate measurement of dialysis dose and an inadequate hemodialysis prescription with a predictably poor clinical outcome. Allowance for compartment effects is particularly important in patients receiving treatment with a high ratio of dialyzer clearance to total body water, now commonly encountered during short-time, high-efficiency dialysis.