Gitelman syndrome and glomerular proteinuria: a link between loss of sodium-chloride cotransporter and podocyte dysfunction?
Gitelman syndrome and glomerular proteinuria: a link between loss of sodium-chloride cotransporter and podocyte dysfunction?
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DOI：
10.1093/ndt/gfu075
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发表时间：
2014-09-01
影响因子：
6.1
通讯作者：
Devuyst, Olivier
中科院分区：
文献类型：
--
作者：
Demoulin, Nathalie;Aydin, Selda;Devuyst, Olivier
我们报告一个27岁的病人，表现为慢性低钾血症，不适当的钾尿，低镁血症和尿潴留，伴有中度蛋白尿。遗传分析证明编码钠氯化物协同转运蛋白（NCC）的SLC 12 A3基因中存在纯合突变（p.Arg 399 Cys），证实了Gitelman综合征的诊断。进一步的基因检测没有显示NPHS2的任何突变。考虑到与蛋白尿的异常相关性，进行了肾活检。光学显微镜下可见肾小球器肥大和系膜增厚。除了可能的局灶性节段性肾小球硬化病变，电子显微镜检查显示广泛的节段性增厚的肾小球基底膜（GBM），与节段性规则GBM的低范围厚度和足细胞足突消失形成对比。有趣的是，GBM的改变也在Gitelman综合征的Slc12a3敲除小鼠模型中观察到。这些数据表明Gitelman综合征和GBM继发性改变之间的关联可能不是巧合。可能的机制包括血管紧张素II或肾素诱导的足细胞病变，以及慢性低钾血症。
We report on a 27-year-old patient presenting with chronic hypokalaemia, inappropriate kaliuresis, hypomagnesaemia and alkalosis, associated with moderate proteinuria. Genetic analysis evidenced a homozygous mutation (p.Arg399Cys) in the SLC12A3 gene coding for the sodium-chloride cotransporter (NCC), confirming the diagnosis of Gitelman syndrome. Further genetic testing did not show any mutation in NPHS2. A renal biopsy was performed in view of the unusual association with proteinuria. Light microscopy showed hypertrophy of the juxtaglomerular apparatus and discrete mesangial thickening. In addition to possible focal segmental glomerular sclerosis lesions, electron microscopy showed extensive segments of variably thickened glomerular basement membrane (GBM), contrasting with segments of regular GBM of low range thickness, and effacement of podocyte foot processes. Of interest, alterations of the GBM were also observed in a Slc12a3 knock-out mouse model for Gitelman syndrome. These data suggest that the association between Gitelman syndrome and secondary changes of the GBM is probably not coincidental. Possible mechanisms include angiotensin II- or renin-induced podocyte lesions, as well as chronic hypokalaemia.