Urea kinetics in healthy women during normal pregnancy.

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.

Comparison of urinary 5-L-oxoproline (L-pyroglutamate) during normal pregnancy in women in England and Jamaica.

Urinary 5-L-oxoproline was measured during normal pregnancies in Southampton, England and Kingston, Jamaica. The CV of 5-L-oxoproline excretion in urine, determined over 7 d in a non-pregnant woman and three pregnant women, was 10-36%. Compared with non-pregnant women, urinary 5-L-oxoproline increased three to four times from early pregnancy in women in Southampton, a highly significant difference, and remained elevated at similar levels during mid and late pregnancy. For women in Kingston, the excretion of 5-L-oxoproline was similar to that of Southampton women in the non-pregnant group and during early pregnancy. However, there was a progressive increase in the excretion of 5-L-oxoproline as pregnancy advanced and by late pregnancy excretion was from three to ten times greater than the average for the non-pregnant women. There was a significant difference between the women in Southampton and the women in Kingston during mid and late pregnancy, with women in Kingston excreting twice as much 5-L-oxoproline during late pregnancy. If the excretion of 5-L-oxoproline is a measure of glycine insufficiency, the results would indicate that in some pregnancies the ability of the mother to provide glycine for herself and the developing fetus is marginal or inadequate and the constraint appears more marked in Jamaica than in England.

Urea kinetics in healthy women during normal pregnancy

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 significantly inverse linear relationship overall for hydrolysis as a proportion of production and excretion as 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.(AU)

Comparison of urinary 5-L-oxoproline (L-pyroglutamate) during normal pregnancy in women in England and Jamaica

Urinary 5-L-oxoproline was measured during normal pregnancies in Southampton, England and Kingston, Jamaica. The CV of 5-L-oxoproline excretion in urine, determined over 7 d in a non-pregnant woman and three pregnant women, was 10-36 percent. Compared with non-pregnant women, urinary 5-L-oxoproline increased three to four times from early pregnancy in women in Southampton, a highly significant difference, and remained elevated at similar levels during mid and late pregnancy. For women in Kingston, the excretion of 5-L-oxoproline was similar to that of Southampton women in the non-pregnant group and during early pregnancy. However, there was a progressive increase in the excretion of 5-L-oxoproline as pregnancy advanced and by late pregnancy excretion was from three to ten times greater than the average for the non-pregnant women. There was a significant difference between the women in Southampton and the women in Kingston during mid and late pregnancy, with women in Kingston excreting twice as much 5-l-oxoproline during late pregnancy. If the excretion of 5-L-oxoproline is a measure of glycine insufficiency, the results would indicate that in some pregnancies the ability of the mother to provide glycine for herself and the developing fetus is marginal or inadequate and the constraint appears more marked in Jamaica than in England.(AU)

Urea kinetics in healthy young women: minimal effect of stage of menstrual cycle, contraceptive pill and protein intake.

Urea kinetics were measured using prime/intermittent oral doses of [15N15N]urea, on five separate protocols in thirteen normal young women. Each woman underwent either two or three study protocols. Measurements were made at day 12 and day 22 of the menstrual cycle, whilst consuming their habitual protein intake in seven women not taking the contraceptive pill and in six women taking the contraceptive pill. In three women taking the pill, and three not taking the pill, urea kinetics were measured whilst taking a diet in which the intake was restricted to 55 g protein/d. There was no difference in the rate of urea production, urea excretion or urea hydrolysis between the women taking the pill and those not taking the pill at day 22. In the women not taking the pill there was no difference in any measure between day 12 and day 22. In the women taking the pill there was a significant difference in the disposal of urea N to excretion or hydrolysis on day 12 compared with day 22, with a relative decrease in excretion and enhancement of hydrolysis at day 12 compared with day 22. On the restricted diet, an intake of 55 g protein/d represented 77% of the habitual intake and urea production, excretion and hydrolysis were reduced to about 84% of the rate found on the habitual intake. In paired studies the reduction in urea production was statistically significant, and there was a statistically significant linear relationship between urea production and either intake or the sum of intake plus hydrolysis. The within-individual variability for urea production was about 10%, for excretion 15% and for hydrolysis 44%. The between-individual variability for intake was about 17% on the habitual intake. The variability for production, excretion and hydrolysis (14, 13, 36%) was less in the women not taking the contraceptive pill than in those taking the pill 23, 32, 42% respectively). The variability was reduced on the controlled low intake of 55 g protein compared with the habitual intake. These results confirm the wide variability in aspects of urea kinetics between individuals. In women this variability is not, to any large extent, accounted for by changes associated with the menstrual cycle.

PIP: In England, nutritionists measured urea kinetics in 13 women aged 21-37 years who took prime/intermittent oral doses of [15N15N]urea under five separate conditions to identify the extent to which the stage of the menstrual cycle and the use of a low-dose estrogen oral contraceptive (OC) contribute to variability. The protocols included habitual diet alone and urea measurement on either day 12 or day 22 of the menstrual cycle, habitual diet and OC use with urea measurement on either day 12 or day 22, a diet of 55 g protein/day (around 77% of habitual intake) with no control over day of urea measurement, and a diet of 55 g protein/day and OC use with no control over day of urea measurement. The habitual diet had little effect on urea kinetics of the time of the menstrual cycle. OC use also had little effect, except it did decrease excretion (107 vs. 132 mg N/kg/day for non-use) and increase hydrolysis (97 vs. 62 mg N/kg/day) of urea at day 12 of the menstrual cycle. The 55 g/day protein intake decreased urea production, excretion, and hydrolysis (about 84% of habitual diet). It effected the least variation among individuals. For all protocols, the variation in plateau enrichment for urea was 11.8%. The within-individual variability stood at around 10% for urea production, 15% for excretion, and 44% for hydrolysis. For intake, the between-individual variability was around 17% on habitual intake. Nonusers exhibited less variability for production, excretion, and hydrolysis than OC users. In the paired studies, the reduction in urea production and the linear relationship between urea production and either intake or the sum of intake plus hydrolysis was statistically significant. These findings show that healthy young women have urea kinetics similar to those of men and that there is wide variability in urea kinetics between individuals.