The Renal Excretion of Nutrients in Pregnancy

Abstract

SummaryA feature of normal pregnancy is a huge increase in the excretion of nutrients in urine. Glycosuria is commonplace, and about half of all healthy pregnant women excrete more than when not pregnant. Amounts in excess of 1 g/24 hr are common, and excretion is characteristically intermittent with little apparent relation to plasma levels. Amino acid excretion is also raised four or five times by late pregnancy, with a characteristic pattern for different amino acids, and folate and other water soluble vitamins are similarly squandered. The mechanisms are not understood.THE retention during evolution of an excretory system based on massive blood filtration required the simultaneous development, at least for land animals, of an extremely efficient system for the recovery of blood constituents which the organism could not afford to discard. In general, the recovery arrangements are highly efficient; for example, something of the order of 150 g of glucose will be filtered through the glomeruli daily by the average person, and yet no more than about 100 mg escapes into the urine, an efficiency of more than 99 9°/.The kidneys are subjected throughout normal pregnancy to a greatly increased plasma flow, more than 700 ml/min compared to a non-pregnant average of less than 500 ml/min, and the glomerular filtration rate rises in parallel, from less than 100 ml/min to about 150 ml/min for the whole of pregnancy. The filtered load of nutrients presented to the tubules in pregnancy, allowing for the fact that the plasma concentration of most nutrients is reduced, is therefore up to 40°/ greater than before pregnancy, but an increase of that size is well within the capacity of the tubules, and it is one of the more bizarre and unexpected features of normal pregnancy that relatively large quantities of filtered nutrients are discarded in the urine. GlucoseThat the pregnant woman commonly excretes detectable glucose in her urine has been recognized for more than a century, and during the 1920s the provocation of glycosuria by an oral sugar load, or even by a small dose of phlorizin, enjoyed a vogue as a pregnancy test. In a recent study of thirty healthy normal pregnant women, Lind & Hytten (1972), measured glucose excretion in 24 hr collections of urine, made at intervals from early pregnancy and again 6 weeks post partum. There were large differences, both between women and often in the same woman from time to time. In the non-pregnant (post partum) state all women remained within the usual non-pregnant limit of about 140 mg in 24 hr and four remained within that limit during their pregnancy; the remainder exceeded normal nonpregnant limits during pregnancy; twelve ranged up to 500 mg, four up to 1000 mg, and the other ten excreted more than 1 g in 24 hr, with one reaching almost 10 g in one 24 hr collection. In general, there was great irregularity from time to time and, although glycosuria tended to be greater in late pregnancy than in early pregnancy, five of the thirty women showed

Following Healthy Pregnancy by Nuclear Magnetic Resonance (NMR) Metabolic Profiling of Human Urine

“…Notably, the changes listed in Table 2 include some detected for the first time to our knowledge in maternal urine, in a pregnancy context, namely those regarding: choline, creatinine, 4-DEA and 4-DTA, furoylglycine, GAA, 3-HBA, and lactate (noted as f in Table 2). Furthermore, an increase was found here for leucine, contrary to other reports indicating decreased excretion late in pregnancy; 28,29 however, our observation is actually in agreement with an earlier report. 40 In addition, the four still unassigned resonances (U1 to U4) play an important role in defining the compositional profile of maternal urine throughout pregnancy, particularly U1 and U2, which have significant variation between NP and f1st T (pvalue ≈ 10 −6 ), and between 2nd and 3rd T (p-value ≈ 10 −7 ).…”

“…In relation to urine, increased excretion of carnitines has been seen in the 1st T, followed by a decrease thereafter, 27 whereas other targeted studies have detected increased excretion of several amino acids, glucose, and folate. 28,29 However, no overall metabolite profiling of maternal urine has been performed, to our knowledge, as a function of pregnancy progression. This work describes, for the first time to our knowledge, an untargeted 1 H NMR study of urine collected for healthy nonpregnant and first, second, and third trimester pregnant women, to evaluate the dynamic metabolic adaptations of healthy pregnancies.…”

Second Trimester Maternal Urine for the Diagnosis of Trisomy 21 and Prediction of Poor Pregnancy Outcomes

“…Amino acid changes may reflect their selective use as gluconeogenesis substrates, possibly preferentially for Ala, Lys, and Tyr (less excreted), compared to Ile and Thr. Other changes include higher excretion of N -methyl-nicotinamide (NMND) (nucleotide metabolism), lower excretion of succinate (possibly diverted to the fetus, in agreement with increased levels in AF), and higher lactose excretion, seen in pregnant healthy women , but not in relation to prenatal disorders. CNS malformations seem characterized by a change in the acetyl-carnitine/carnitine balance, reflecting somewhat higher circulating acetyl-CoA levels and an underuse of carnitine, possibly reflecting a relatively lower level of lipid oxidation compared to other FM types.…”

Obstetric Nephrology

“…Despite the increased GFR that accompanies pregnancy, studies that utilized a continuous intravenous glucose challenge with inulin clearance techniques did not document a difference in GFR between women who displayed glycosuria and those who did not, suggesting instead that the maximal tubular reabsorption capacity was significantly decreased in pregnant women who displayed glycosuria (54-56). The precise incidence, however, of glycosuria in pregnancy is unclear, with extensive variability noted between women and even in the same woman at different times during pregnancy (56,57). The largest study to date, a retrospective chart assessment of 17,647 pregnancies with normal carbohydrate screening, noted an incidence of only 1.6% on routine clinical screening (58).…”

“…Furthermore, no relationship of glycosuria to clinical diabetes has been demonstrated, because the majority of women who demonstrate glycosuria have normal glucose tolerance, and even obviously diabetic pregnant women do not consistently demonstrate glycosuria. A similarly confusing pattern has emerged for increased urinary excretion of amino acids and water-soluble vitamins (57,59). The few studies designed to determine mechanisms were inconclusive and noted patterns of excretion were not related to the biologic function or chemical structure of the compound (59).…”