Increases in Urinary Inhibitor Activity and Excretion of an Inhibitor of Crystalluria in Pregnancy: A Defense Against the Hypercalciuria of Normal Gestation

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Abstract
Supplemental dietary calcium (2 gm/day) is recommended by some to prevent preeclampsia and premature labor. There are theoretical concerns, however, that such an approach may precipitate renal stone formation, since most gravidas are hypercalciuric, and their urine is supersaturated with calcium oxalate and phosphate salts. The present serial study of 8 healthy normotensive women at 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36+ weeks of pregnancy, and 12 weeks postpartum, was designed to assess the effects of gestation on urinary factors which inhibit stone formation. By gestational weeks 4 and 8, 24 hour creatinine clearances and calcium excretion, respectively, increased significantly, the former peaking by week 12, while the latter continued to rise and was 2.5-fold greater near term. Urinary inhibitor activity (14C oxalic acid incorporation into seed crystals) also increased significantly (27% near midpregnancy, remaining elevated till delivery). There was a striking increment of the glycoprotein crystallization inhibitor nephrocalcin, measured by a specific ELISA assay, which rose significantly by week 8, and was 20-fold higher near term. All values normalized 12 weeks postpartum. In other studies we determined that the amino acid composition and dissociation constant of nephrocalcin excreted in pregnancy was very similar to those of the glycoprotein inhibitor purified from the urine of nonpregnant adults. We conclude from these data that hypercalciuric gravidas with urine manifesting a high potential for crystallization are protected from stone formation, perhaps due to enhanced excretion of inhibitory proteins. Further studies are needed to ascertain if this protection is sufficient when the hypercalciuria is augmented by calcium loading.

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