Tracer methods underestimate short-term variations in urea production in humans. Hamadeh, Mazen J., and L. John Hoffer. School of Dietetics and Human Nutrition, and McGill Nutrition and Food Science Centre, McGill University, Montreal, Quebec H3A 1A1 Canada
APStracts 4:0278E, 1997.
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 unlabelled urea to assess the accuracy of this technique in normal, postabsorptive men under 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 unlabelled urea was infused from hours 4-12 at a rate 2-fold greater than the endogenous production rate ("step" infusion); (3) tracer 13C -urea was infused for 12 h, and unlabelled urea was infused from hours 4-8 ("pulse" infusion); and (4) tracer 13C-urea was infused for 9 h, and unlabelled alanine was infused at a rate of 120 mg/kg.h (1.35 mmol/kg.h) from hours 4-9. Urea Ra was calculated using (a) the isotopic steady state equation (i/TTR), (b) Steele's nonsteady state equation, and (c) 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-hour step and 4-hour pulse unlabelled urea infusions, Steele's nonsteady state equation underestimated true urea input by 22% (step) and 33% (pulse); whereas the nonisotopic method underestimated it by 28% (step) and 10% (pulse). Similar conclusions derived from the alanine infusion. These results indicate that while Steele's nonsteady state equation and the nontracer method more accurately predict total urea Ra than the steady state equation, they nevertheless seriously underestimate it for as long as 8 h after a change in true urea Ra.

Received 14 July 1997; accepted in final form 9 December 1997.
APS Manuscript Number E326-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 January 1998