The Pharmacological Characteristics of Molecular-Based Inherited Salt-Losing Tubulopathies
The Pharmacological Characteristics of Molecular-Based Inherited Salt-Losing Tubulopathies
复制标题
DOI：
10.1210/jc.2010-0392
复制
发表时间：
2010-12-01
影响因子：
5.8
通讯作者：
Matsuo, Masafumi
中科院分区：
文献类型：
--
作者：
Nozu, Kandai;Iijima, Kazumoto;Matsuo, Masafumi
背景：随着分子遗传学的最新进展，我们对遗传性失盐小管病的了解有所改善。然而，Bartter综合征和Gitelman综合征的术语并不总是准确反映其病理生理基础或临床表现，有些患者难以从其临床表现进行诊断。目的：在本研究中，我们对遗传性失盐小管病患者进行分子分析和利尿试验，以阐明这些疾病的药理学特征。患者：我们对16例失盐小管病变患者（2例SLC12A1患者，2例KCNJ1患者，9例CLCNKB患者，3例SLC12A3患者）检测突变并随后使用速尿和噻嗪进行利尿试验。结果：SLC12A1突变的患者对呋塞米无反应，而SLC12A3突变的患者对噻嗪无反应。然而，CLCNKB突变的患者对噻嗪没有反应，对呋塞米的反应正常，而KCNJ1突变的患者对这两种利尿剂都有良好的反应。本研究揭示了这些疾病的以下特征：1)CLCNKB突变的受试者表现出一种或多种Gitelman综合征的生化特征（包括低镁血症、低钙尿症和对噻嗪类药物不敏感的部分氯排泄）；2) KCNJ1突变的受试者对呋塞米和噻嗪类药物的部分氯排泄表现出正常的敏感性。结论：这些结果表明，即使使用利尿剂，这些疾病在一些患者中也难以区分。本临床报告提供了重要的发现，可以提高我们对遗传性失盐小管病和肾小管生理的理解。[J] .中华内分泌杂志，2010,25(5):511- 518。
Context: Our understanding of inherited salt-losing tubulopathies has improved with recent advances in molecular genetics. However, the terminology of Bartter syndrome and Gitelman syndrome does not always accurately reflect their pathophysiological basis or clinical presentation, and some patients are difficult to diagnose from their clinical presentations.Objective: In the present study, we conducted molecular analysis and diuretic tests for patients with inherited salt-losing tubulopathies to clarify the pharmacological characteristics of these disorders.Patients: We detected mutations and subsequently conducted diuretic tests using furosemide and thiazide for 16 patients with salt-losing tubulopathies (two with SLC12A1; two with KCNJ1; nine with CLCNKB; and three with SLC12A3).Results: Patients with SLC12A1 mutations showed no response to furosemide, whereas those with SLC12A3 mutations showed no response to thiazide. However, patients with CLCNKB mutations showed no response to thiazide and a normal response to furosemide, and those with KCNJ1 mutations showed a good response to both diuretics. This study revealed the following characteristics of these disorders: 1) subjects with CLCNKB mutations showed one or more biochemical features of Gitelman syndrome (including hypomagnesemia, hypocalciuria, and fractional chloride excretion insensitivity to thiazide administration); and 2) subjects with KCNJ1 mutations appeared to show normal fractional chloride excretion sensitivity to furosemide and thiazide administration.Conclusions: These results indicate that these disorders are difficult to distinguish in some patients, even when using diuretic challenge. This clinical report provides important findings that can improve our understanding of inherited salt-losing tubulopathies and renal tubular physiology. (J Clin Endocrinol Metab 95: E511-E518, 2010)