It is well established that in human subjects a proportion of urea production undergoes hydrolysis in the gastrointestinal tract with release of N potentially available for amino acid synthesis. Previous studies have suggested adaptive changes in urea kinetics, with more urea-N retained within the metabolic pool during reduced dietary intakes of energy and protein. We therefore investigated the effect of rate and extent of weight loss on adaptive changes in urea kinetics in two groups (each n 6) of obese men (mean age 43 (sd 12) years, BMI 34·8 (sd 2·9)kg/m2) during either total starvation for 6d or a very-low-energy diet (2·55MJ/d) for 21d. Subjects were resident in the Human Nutrition Unit of the Rowett Research Institute (Aberdeen, Scotland, UK) and lost 6 and 9% initial body weight within the starvation and dieting groups respectively. Changes in urea-N metabolism were assessed by stable isotope tracer kinetics using [15N15N]urea infused intravenously for 36h before, during and after weight loss. In response to weight loss, urea production decreased (P<0·01) by 25% from 278 to 206μmol urea-N/h per kg within the dieting group only. However, no changes were observed in the proportion of urea being hydrolysed in the gastrointestinal tract (range 20–25%) or in the proportion of N retained for anabolic purposes (80–85% urea-N from gastrointestinal hydrolysis) within either group. It was concluded that no adaptive changes in urea kinetics occurred in response to either the different rate or extent of weight loss.

The effect of two levels of dietary protein energy, moderate (20 %; MP) and high (70 %; HP), on urea kinetics in eleven domestic cats was studied. After a 3-week prefeed, a single dose of [15N15N]urea was administered, and urine and faeces collected over the subsequent 5 d. For each 24 h period, total urea and enrichment of [15N15N]- and [15N14N]urea in urine were determined, and a model applied to calculate urea production, entry into the gastrointestinal tract, recycling to urine or faeces and, by difference, retention by the body and potentially available for anabolism. Urea production and excretion increased with dietary protein level (P<0·05). Most of the urea produced was excreted, with only a small proportion entering the gut, and with the pattern of urea disposal not significantly different between the HP and MP diets. Thus, the percentages of urea production available to the gut were 15 % (MP) and 12 % (HP), of which 57 % (MP) and 59 % (HP) was recycled in the ornithine cycle, 40 % (MP and HP) was potentially available for anabolism and the rest lost as faecal N. As a percentage of urea produced the amount potentially available for anabolism was very low at 6·41 % (MP diet) and 4·79 % (HP diet). In absolute terms urea entering the gut, being recycled in the ornithine cycle and potentially available for anabolism was significantly higher on the HP diet (P<0·05). These results show that cats operate urea turnover, but at a lower rate, and with less nutritional sensitivity than has been reported for other species.

Urea kinetics were measured in normal women aged 22-34 years at weeks 16, 24 and 32 on either their habitual protein intake (HABIT.) or a controlled intake of 60 g protein/d (CONTROL), using primed-intermittent oral doses of [15N15N]urea and measurement of plateau enrichment in urinary urea over 18 h (ID) or a single oral dose of [15N15N]urea and measurement of enrichment of urea in urine over the following 48 h (SD). The intake of protein during HABIT-ID (80 g/d) was greater than that on HABIT-SD (71 g/d); urea production as a percentage of intake was significantly greater at week 16 for HABIT-ID than HABIT-SD, whereas urea hydrolysis at week 16 was greater for HABIT-SD than HABIT-ID and urea excretion at week 32 was greater for HABIT-ID than HABIT SD. The combined results for HABIT-ID and HABIT-SD showed a significant reduction in urea production at week 32 compared with week 24. Urea excretion decreased significantly from week 16 to week 24 with no further decrease to week 32 and urea hydrolysis was significantly greater at week 24 than either week 16 or week 32. Compared with HABIT, on CONTROL there was a decrease in urea production at week 16, and urea excretion was significantly reduced at week 16. For all time periods urea production was closely related to the sum of intake plus hydrolysis. Hydrolysis was greatest at week 24 and closely related to urea production. There was a significant inverse linear relationship overall for hydrolysis as a proportion of production and excretion as a proportion of intake. The results show that on HABIT N is more effectively conserved in mid-pregnancy through an increase in urea hydrolysis and salvage, and during late pregnancy through a reduction in urea formation. Lowering protein intake at any stage of pregnancy increased the hydrolysis and salvage of urea. The staging of these changes was later than that in pregnancy in Jamaica.

The kinetics of urea metabolism were measured in children recovering from severe malnutrition. For a period of up to 10 d they received one of four diets which provided 711 kJ (170 kcal)/kg per d. Two groups received a diet with a high protein: energy (P:E) ratio of 10.6% (HP), enriched with either fat (HP/F) or maize starch and sucrose (HP/C). Two groups received a diet with a low P:E ratio of 8.8% (LP), enriched with either fat (LP/F) or maize starch and sucrose (LP/C). The rate of weight gain on the HP diets was significantly greater than on the LP diets. There was no difference in urea production between any of the four diets: HP/F 1.23 (SE 0.12), HP/C 1.37 (SE 0.14), LP/F 1.64 (SE 0.22), LP/C 1.15 (SE 0.15) mmol nitrogen/kg per h. On the HP diets urea excretion was 0.77 (SE 0.07) mmol N/kg per h. 61 % of production. There was significantly less urea excreted in the urine on diet LP/C than on LP/F (0.36 (SE 0.05) and 0.64 (SE 0.04) mmol N/kg per h respectively). A significantly greater percentage of the urea production was hydrolysed on the LP diets (61 %) compared with the HP diets (39 %), with the consequence that 50% of urea-N produced was available for synthetic activity on the LP diets compared with 30% on the HP diets. The increase in the urea hydrolysed on the LP diets was equivalent in magnitude to the decreased intake of N, so that overall intake plus hydrolysis did not differ between the LP and the HP diets. Crude N balance was similar on diets HP/F, HP/C and LP/C, but was significantly reduced on diet LP/F. These results show that there is an accommodation in urea kinetics during rapid catch-up weight gain, which becomes evident when the P:E ratio of the diet falls to 8.8%. It is proposed that, for a P:E ratio of 8.8%, protein is limiting for catch-up growth. When the intake has a P:E ratio of 8.8% the pattern of urea kinetics can be modified by the relative proportions of fat and carbohydrate in the diet. The measurement of urea kinetics provides a useful approach to the definition of the adequacy of the protein in the diet.