TRACER METHODS UNDERESTIMATE SHORT-TERM VARIATIONS IN UREA PRODUCTIONIN HUMANS

Urea production rate (R-a) is commonly measured using a primed continu ous tracer urea infusion, but the accuracy of this method has not been clearly established in humans. We used intravenous infusions of unlab eled urea to assess the accuracy of this technique in normal, postabso rptive men under the following four different conditions: 1) tracer [C -13]urea was infused under basal conditions for 12 h (control); 2) tra cer [C-13]urea was infused for 12 h, and unlabeled urea was infused fr om hours 4 to 12 at a rate twofold greater than the endogenous R-a ('' step'' infusion); 3) tracer [C-13]urea was infused for 12 h, and unlab eled urea was infused from hours 4 to 8 (''pulse'' infusion); and 4) t racer [C-13]urea was infused for 9 h, and unlabeled alanine was infuse d at a rate of 120 mg.kg(-1).h(-1) (1.35 mmol.kg(-1).h(-1)) from hours 4 to 9. Urea R-a was calculated using the isotopic steady-state equat ion (tracer infusion rate/tracer-to-tracee ratio), Steele's non-steady -state equation, and urinary urea excretion corrected for changes in t otal body urea. For each subject, endogenous urea R-a 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 condi tions, urea R-a at hour 4 was similar to that measured at hour 12. Aft er 8-h step and 4-h pulse unlabeled urea infusions, Steele's non-stead y-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 n on-steady-state equation and the nontracer method more accurately pred ict total urea R-a than the steady-state equation, they nevertheless s eriously underestimate total urea R-a for as long as 8 h after a chang e in true urea R-a.