Evaluation of urea kinetics utilizing stable isotope urea and pharmacokinetic modeling

The determination of urea kinetics plays a central role in clinical dialysi s prescription. There persist, however, significant limitations to current approaches, particularly as they pertain to rigorous explorations of urea m etabolism, distribution, and removal. This report describes methodologies d esigned to address these limitations by coupling a stable nitrogen isotope method with strict compartmental pharmacokinetic modeling. The findings of the present study can be summarized as follows. First, the use of stable is otope labeled exogenous urea is a reliable clinically applicable method for determination of urea kinetics. Second, this method offers significant adv antages in that it allows for an accurate measurement of urea distribution space, endogenous urea production, and non-renal clearance of urea. Third, this method is significantly more rigorous than urea kinetic models that ut ilize only endogenous urea and do not carefully fit data points. Finally, p harmacokinetic modeling suggests that a two-compartment model satisfies all aspects of urea distribution and removal, but these compartments should no t be equated with specific physiologic spaces. The combination of stable is otope urea compartmental modeling is a rigorous methodology for the assessm ent and validation of urea kinetics.