Measurement of urea kinetics in humans: a validation of stable isotope tracer methods.

To define the importance of an accurate priming dose for measurement of urea production using a primed, short-duration (e.g., 4 h) infusion of labeled urea, [18O]- and [13C]ureas were infused simultaneously at two different prime-to-infusion (P/I) doses into five young adult men. The measured mean (+/-SE) urea production rates were 261 +/- 12 and 509 +/- 25 mumol X kg-1 X h-1 for P/I = 12.6-h and 5.0-h priming doses, respectively. In a second series of studies, a single dose of [18O]urea tracer was administered intravenously to four subjects, and the urea production rate was determined from the plasma urea tracer disappearance curve obtained over the following 6 h by fitting the data to a two-exponent curve. The mean urea production rate was 224 +/- 14 mumol X kg-1 X h-1. Because the fractional turnover of the body urea pool is slow, the priming dose strongly influences the "apparent" plasma urea enrichment plateau and, therefore, the measured urea production rate during short-duration infusions. Alternatively, the single-dose protocol can be applied to measure human urea production accurately in periods as short as 6 h.