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School of Dietetics and Human Nutrition and McGill Nutrition and Food Science Centre, McGill University, Montreal, Quebec, Canada H3A 1A1
Urea production rate
(Ra) is commonly measured using
a primed continuous tracer urea infusion, but the accuracy of this
method has not been clearly established in humans. We used intravenous infusions of unlabeled urea to assess the accuracy of this technique in
normal, postabsorptive men under the following four different conditions: 1) tracer
[13C]urea was infused
under basal conditions for 12 h (control); 2) tracer
[13C]urea was infused
for 12 h, and unlabeled urea was infused from hours
4 to 12 at a rate
twofold greater than the endogenous
Ra ("step" infusion);
3) tracer
[13C]urea was infused
for 12 h, and unlabeled urea was infused from hours
4 to 8 ("pulse"
infusion); and 4) tracer
[13C]urea was infused
for 9 h, and unlabeled alanine was infused at a rate of 120 mg · kg
1 · h1
(1.35 mmol · kg1 · h1)
from hours 4 to
9. Urea
Ra was calculated using the
isotopic steady-state equation (tracer infusion rate/tracer-to-tracee
ratio), Steele's non-steady-state equation, and urinary urea excretion corrected for changes in total body urea. For each subject, endogenous urea Ra was measured at
hour 4 of the basal condition, and the sum of this rate plus exogenous urea input was considered as "true urea input." Under control conditions, urea
Ra at hour
4 was similar to that measured at hour
12. After 8-h step and 4-h pulse unlabeled urea
infusions, Steele's non-steady-state equation underestimated true urea
input by 22% (step) and 33% (pulse), whereas the nonisotopic method
underestimated true urea input by 28% (step) and 10% (pulse). Similar
conclusions were derived from the alanine infusion. These results
indicate that, although Steele's non-steady-state equation and the
nontracer method more accurately predict total urea
Ra than the steady-state equation,
they nevertheless seriously underestimate total urea
Ra for as long as 8 h after a
change in true urea Ra.
tracer kinetics; stable isotopes; fed state
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