The consequences of physiological resistances on metabolite removal from the patient-artifical kidney system

A diffusion limited, multicompartment patient-artifical kidney transport model has been developed. The physiological transport parameters have been clincially elevated for radiosotopically tagged urea, creatinine, uric acid, vitamin B12, and inulin with anuric, chronic uremic patients. Concomitant hemodialysis simulations illustrate that a 3 compartment patient model is adequate to characterize physiological transport. However, because of the high value of the transcapillary mass transfer coefficient, it is concluded that a 2 compartment (intracellular/extracellular) model is adequate to define mass transfer in the patient-artifical kidney system: a single pool may be assumed for very low hemodialyzer (less than 20 ml/min) clearances. Dialysis simulations also demonstrate that a point of diminshing returns is reached with respect to increasing mass removal from the patient, via increasing dialyzer clearance for middle molecules. In a 5 hr hemodialysis simulation the system becomes limited by physiological mass transfer resistances for dialyzer clearances greater than 100 ml/min. It is concluded that physiological transport resistances significantly impeded the removal of middle molecules from the patient-artifical kidney system. As a result, a single, well mixed pool assumption is not generally adequate to describe solute transport. A consequence of this conclusion is that the M2-hr hypothesis, which is based on a single pool assumption, cannot be generally utilized to accurately adjust hemodialysis treatment schedules for equivalent middle molecule removal. We are currently analyzing the patient-artifical kidney system to define improved adjustments modes for equivalent mass removal employing a 2 pool patiemt model.