Nephrology Section MC 5100, Univ. of Chicago Medicine, 5841 South Maryland Ave., Chicago, IL 60637.
Am J Physiol Renal Physiol. 2013 Sep 15;305(6):F853-60. doi: 10.1152/ajprenal.00124.2013. Epub 2013 Jul 17.
Patients with idiopathic hypercalciuria (IH) have decreased renal calcium reabsorption, most marked in the postprandial state, but the mechanisms are unknown. We compared 29 subjects with IH and 17 normal subjects (N) each fed meals providing identical amounts of calcium. Urine and blood samples were collected fasting and after meals. Levels of three candidate signalers, serum calcium (SCa), insulin (I), and plasma parathyroid hormone (PTH), did not differ between IH and N either fasting or fed, but all changed with feeding, and the change in SCa was greater in IH than in N. Regression analysis of fractional excretion of calcium (FECa) was significant for PTH and SCa in IH but not N. With the use of multivariable analysis, Sca entered the model while PTH and I did not. To avoid internal correlation we decomposed FECa into its independent terms: adjusted urine calcium (UCa) and UFCa molarity. Analyses using adjusted Uca and unadjusted Uca parallel those using FECa, showing a dominant effect of SCa with no effect of PTH or I. The effect of SCa may be mediated via vitamin D receptor-stimulated increased abundance of basolateral Ca receptor, which is supported by the fact PTH levels also seem more responsive to serum Ca in IH than in N. Although our data support an effect of SCa on FECa and UCa, which is more marked in IH than in N, it can account for only a modest fraction of the meal effect, perhaps 10-20%, suggesting additional mediators are also responsible for the exaggerated postprandial hypercalciuria seen in IH.
特发性高钙尿症（IH）患者的肾钙重吸收减少，在餐后最为明显，但机制尚不清楚。我们比较了 29 名 IH 患者和 17 名正常对照者（N），他们分别接受了提供相同钙量的膳食。空腹和餐后采集尿液和血液样本。空腹和进食时，IH 和 N 患者的血清钙（SCa）、胰岛素（I）和血浆甲状旁腺激素（PTH）水平均无差异，但均随进食而变化，且 IH 患者的 SCa 变化大于 N。IH 患者的 PTH 和 SCa 对钙排泄分数（FECa）的回归分析有显著意义，但 N 患者无此作用。采用多变量分析，SCa 进入模型，而 PTH 和 I 未进入。为避免内部相关性，我们将 FECa 分解为其独立项：校正后的尿钙（UCa）和 UFCa 摩尔浓度。使用校正后的 UCa 和未校正的 UCa 进行的分析与使用 FECa 的分析相似，表明 SCa 具有主导作用，而 PTH 或 I 没有作用。SCa 的作用可能是通过维生素 D 受体刺激增加基底外侧 Ca 受体的丰度来介导的，这一事实支持 PTH 水平在 IH 中对血清 Ca 的反应似乎也比 N 更敏感。尽管我们的数据支持 SCa 对 FECa 和 UCa 的影响，且 IH 比 N 更明显，但它只能解释进餐效应的一小部分，可能为 10-20%，提示还有其他介质也负责 IH 中餐后高钙尿症的夸大作用。
