Hints to the diagnosis of uromodulin kidney disease.
Hints to the diagnosis of uromodulin kidney disease.
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DOI：
10.1093/ckj/sfv110
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发表时间：
2016-02
影响因子：
4.6
通讯作者：
Kawano M
中科院分区：
文献类型：
--
作者：
Onoe T;Yamada K;Mizushima I;Ito K;Kawakami T;Daimon S;Muramoto H;Konoshita T;Yamagishi M;Kawano M
尿调蛋白肾病(UKD)是一种由尿调蛋白基因突变引起的遗传性肾脏疾病。UMOD基因编码Tamm-Horsfall蛋白(THP)，THP是健康人体尿液中含量最丰富的蛋白质。由于UKD的罕见，其发病机制尚未完全阐明。本研究的目的是明确接受肾活检的患者中UKD的发生率。来自肾活检数据库的50岁肾功能不全和高尿酸血症患者进行了THP免疫染色。对可用个体的血清和尿液中THP浓度进行评估。从3787例患者中选择15例进行免疫染色。在三个独立的患者中，观察到肾小管上皮细胞中THP的异常积聚。在三名患者中的两名患者中发现了一种新的错义A247P UMOD突变，其中一名患者有典型的家族性幼年高尿酸血症肾病家族史。所有UMOD A247P突变患者的血、尿THP浓度均显著低于对照组。在目前的研究中，在1,000名接受肾活检的受试者中检测到UKD。然而，在符合上述所有标准的受试者中，有20%(3/15)的患者检测到THP异常积聚，这表明肾活检结合THP免疫染色是诊断UKD的良好工具。此外，在本组受试者中检测到较低的血清THP浓度，可能是一项很好的诊断指标或对了解UKD的发病机制有重要意义。
Uromodulin kidney disease (UKD) is an inherited kidney disease caused by a uromodulin (UMOD) gene mutation. The UMOD gene encodes the Tamm–Horsfall protein (THP), which is the most abundant protein in healthy human urine. Because of its rarity, the incidence of UKD has not been fully elucidated. The purpose of the present study is to clarify the frequency of UKD among patients who underwent renal biopsy. Immunostaining for THP was performed for patients <50 years of age with renal insufficiency and hyperuricemia without overt urinalysis abnormality from renal biopsy databases. Serum and urinary THP concentrations were evaluated in available individuals. Fifteen patients were selected for immunostaining from a total of 3787 patients. In three independent patients, abnormal THP accumulation in renal tubular cells was observed. A novel missense A247P UMOD mutation was detected in two of the three patients, including one having a typical family history of familial juvenile hyperuricemic nephropathy. Serum and urinary THP concentrations of all available patients with UMOD A247P mutation were significantly lower than those of controls. In the present study, UKD was detected in <1 in 1000 subjects who underwent renal biopsies. However, in subjects meeting all of the above criteria, abnormal THP accumulation was detected in 20% (3/15), suggesting that renal biopsy with immunostaining for THP is a good tool for diagnosing UKD. Also, low serum THP concentration detected in the present subjects might be a good diagnostic marker or important in understanding the pathogenesis of UKD.