Leonhardt A, Timmermanns G, Roth B, Seyberth H W
Children's Hospitals, University of Marburg, Germany.
J Pediatr. 1992 Apr;120(4 Pt 1):546-54. doi: 10.1016/s0022-3476(05)82480-1.
Children with hyperprostaglandin E syndrome, a neonatal variant of Bartter syndrome with enhanced renal and systemic formation of prostaglandin E2, have hypercalciuria, nephrocalcinosis, and osteopenia. Because prostaglandin E2 affects tubular calcium handling, stimulates the formation of calcitriol in vitro, and has osteolytic activity, we studied calcium homeostasis and the influence of prostaglandin E2 formation on hypercalciuria in nine patients with hyperprostaglandin E syndrome during long-term indomethacin treatment and after its withdrawal. Suppression of prostaglandin E2 formation by indomethacin resulted in improvement of biochemical and clinical features of hyperprostaglandin E syndrome. However, hypercalciuria, osteopenia, and nephrocalcinosis did not completely resolve. Despite a low calcium diet, daily urinary calcium excretion was enhanced during and after withdrawal of indomethacin treatment (median 6.3, range 5.3 to 14, and median 9.4, range 4.4 to 38 mg/kg per day, respectively). Daily urinary calcium excretion was greater after withdrawal than during indomethacin treatment. Urinary calcium excretion was not correlated with urinary prostaglandin E2 excretion. Plasma levels of intact parathyroid hormone (median 11, range 6.8 to 12 pmol/L) and calcitriol (median 157, range 108 to 236 pg/ml) were elevated during indomethacin treatment and decreased after withdrawal of indomethacin. These data suggest that hypercalciuria in hyperprostaglandin E syndrome is mainly due to a renal leak of calcium, which is caused by enhanced renal formation of prostaglandin E2 and a tubular defect not related to prostaglandin E2 formation. There is no evidence for prostaglandin-stimulated calcitriol formation. Decreasing plasma levels of parathyroid hormone in the presence of renal calcium losses after withdrawal of indomethacin treatment may be due to a bone resorption process caused by systemic prostaglandin formation; the process may contribute to hypercalciuria in the patient not receiving indomethacin.
高前列腺素E综合征是巴特综合征的一种新生儿变异型，其肾脏和全身前列腺素E2的生成增加，患有该综合征的儿童会出现高钙尿症、肾钙质沉着症和骨质减少。由于前列腺素E2会影响肾小管对钙的处理，在体外刺激骨化三醇的形成，并且具有溶骨活性，因此我们研究了9例高前列腺素E综合征患者在长期使用吲哚美辛治疗期间及其停药后钙稳态以及前列腺素E2生成对高钙尿症的影响。吲哚美辛抑制前列腺素E2的生成导致高前列腺素E综合征的生化和临床特征得到改善。然而，高钙尿症、骨质减少和肾钙质沉着症并未完全消除。尽管采用低钙饮食，但在吲哚美辛治疗期间及停药后，每日尿钙排泄量均增加（中位数分别为6.3，范围5.3至14，以及中位数9.4，范围4.4至38mg/kg/天）。停药后的每日尿钙排泄量高于吲哚美辛治疗期间。尿钙排泄与尿前列腺素E2排泄无关。在吲哚美辛治疗期间，血浆完整甲状旁腺激素水平（中位数11，范围6.8至12pmol/L）和骨化三醇水平（中位数157，范围108至236pg/ml）升高，停药后降低。这些数据表明，高前列腺素E综合征中的高钙尿症主要是由于肾脏钙泄漏，这是由肾脏前列腺素E2生成增加和与前列腺素E2生成无关的肾小管缺陷引起的。没有证据表明前列腺素刺激骨化三醇的形成。吲哚美辛治疗停药后存在肾脏钙流失时甲状旁腺激素血浆水平降低可能是由于全身前列腺素形成引起的骨吸收过程；该过程可能导致未接受吲哚美辛治疗的患者出现高钙尿症。
