Reduced urinary excretion of thiazide-sensitive Na-Cl cotransporter in Gitelman syndrome: Preliminary data
Reduced urinary excretion of thiazide-sensitive Na-Cl cotransporter in Gitelman syndrome: Preliminary data
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DOI：
10.1053/j.ajkd.2007.07.022
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发表时间：
2007-11-01
影响因子：
13.2
通讯作者：
Han, Jin Suk
中科院分区：
文献类型：
--
作者：
Joo, Kwon Wook;Lee, Jay Wook;Han, Jin Suk
背景资料：Gitelman综合征（GS）患者SLC 12 A3突变与实际钠-氯（Na-Cl）协同转运蛋白（NCC）表达之间的关系很少被评估。尿噻嗪敏感NCC的检测没有尝试在GS患者中进行。研究设计：病例系列。设置和参与者：6例GS患者和1例隐匿性呕吐患者。结果和测量：肾清除率研究、使用逆转录聚合酶链反应和直接测序进行的SLC 12 A3基因突变分析以及NCC、Na-K-2Cl-协同转运蛋白的免疫组织化学染色，对肾活检标本进行Na+，K+-ATP酶α 1亚基和钙结合蛋白-D-28 K的检测。采用差速离心法分离尿液，用抗人NCC抗体和水通道蛋白2抗体检测。结果：清除率研究结果与GS一致，显示仅使用呋塞米可降低远端氯离子重吸收分数。所有GS患者均存在SLC 12 A3基因突变。免疫组化显示NCC在远曲小管中的表达显著降低，而其他转运蛋白的表达保持完整。尿NCC排泄量显着下降，在GS患者，但不是在病人的surrepented vomiting.Limitations：患者人数少，缺乏突变分析CLCNKB.Conclusions：有NCC表达和突变类型之间没有关系。尿NCC检测有助于GS的鉴别诊断。
Background: The relationship between SLC12A3 mutations and actual sodium-chloride (Na-Cl) cotransporter (NCC) expression in patients with Gitelman syndrome (GS) was rarely evaluated. Detection of urinary thiazide-sensitive NCC was not tried in patients with GS.Study Design: Case series.Setting & Participants: 6 patients with GS and 1 patient with surreptitious vomiting.Outcomes & Measurements: Renal clearance study, mutation analysis using reverse-transcription polymerase chain reaction and direct sequencing for the SLC12A3 gene, and immunohistochemical staining for NCC, Na-K-2Cl-cotransporter, alpha 1-subunit of Na+,K+-ATPase, and calbindin-D-28K of the renal biopsy specimens were performed. Membrane fractions of urine were obtained by using differential centrifugation and probed with antibodies against human NCC and aquaporin 2.Results: Results of clearance studies were consistent with GS, showing decreased distal fractional chloride reabsorption with only furosemide. SLC12A3gene mutations were found in all patients with GS. Immunohistochemistry showed markedly decreased NCC expression in the distal convoluted tubule, whereas expression of other transporters remained intact. Urinary NCC excretion was markedly decreased in patients with GS, but not in the patient with surreptitious vomiting.Limitations: Small number of patients and lack of mutation analysis of CLCNKB.Conclusions: There were no relations between NCC expression and types of mutations. Detection of urinary NCC might be helpful for the differential diagnosis of GS.