Evaluation of urea kinetics utilizing stable isotope urea and pharmacokinetic modeling

The determination of urea kinetics plays a central role in clinical dialysis prescription. There persist, however, significant limitations to current approaches, particularly as they pertain to rigorous explorations of urea metabolism, distribution, and removal. This report describes methodologies designed 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 isotope labeled exogenous urea is a reliable clinically applicable method for determination of urea kinetics. Second, this method offers significant advantages 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 utilize only endogenous urea and do not carefully fit data points. Finally, pharmacokinetic modeling suggests that a two-compartment model satisfies all aspects of urea distribution and removal, but these compartments should not be equated with specific physiologic spaces. The combination of stable isotope urea compartmental modeling is a rigorous methodology for the assessment and validation of urea kinetics.