Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy in patients with the APOE Kyoto mutation
Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy in patients with the APOE Kyoto mutation
复制标题
APOE京都突变患者脂蛋白肾小球病的遗传特征、治疗和预后。
DOI：
10.1038/ki.2013.335
复制
发表时间：
2014-02-01
影响因子：
19.6
通讯作者：
Yang, Yuan
中科院分区：
文献类型：
--
作者：
Hu, Zhangxue;Huang, Songmin;Yang, Yuan
脂蛋白肾小球病是一种罕见的遗传性肾脏疾病，由apoE基因突变引起，以血清apoE升高的蛋白尿和肾病综合征为特征。由于其治疗方法和结果尚不清楚，我们回顾性研究了居住在中国西南同一县的31个无血缘关系的汉族家庭中35名经活检证实为脂蛋白肾小球病的患者。DNA测序在所有患者和28名无症状亲属中检测到apoekyoto突变（p. Arg25Cys）。所有人都有相同的ε3等位基因。患者表现为蛋白尿、总甘油三酯和血清载脂蛋白e水平高于非携带者。无症状携带者血清载脂蛋白e和甘油三酯水平介于患者和非携带者之间。16例患者接受非诺贝特治疗超过12个月。其中6人达到了完全缓解（蛋白尿低于0.3 g/d，血清肌酐稳定），并加强了血脂控制（血清载脂蛋白e和甘油三酯正常值低于100 mg/dl）。其中8人达到部分缓解。在3年的随访中，接受非诺贝特治疗的患者生存率更高，肾功能稳定。因此，非诺贝特可以诱导脂蛋白肾小球病变缓解，而贝特的作用取决于脂质控制程度和基线蛋白尿。此外，血清载脂蛋白e和甘油三酯的正常化可以用来判断降脂治疗的效果。
Lipoprotein glomerulopathy is a rare inherited renal disease, caused by mutation of theAPOEgene, characterized by proteinuria and nephrotic syndrome with elevated serum apoE. Since its treatment and outcome are unknown, we retrospectively studied 35 patients within 31 unrelated Han families with biopsy-proven lipoprotein glomerulopathy residing in the same county in southwest China. DNA sequencing detected theAPOEKyoto mutation (p. Arg25Cys) in all patients and 28 asymptomatic relatives. All shared the same ε3 allele. The patients presented with proteinuria, higher total triglyceride, and serum apoE levels relative to non-carriers. The serum apoE and triglyceride levels of asymptomatic carriers were between those of the patients and non-carriers. Sixteen patients received fenofibrate treatment for over 12 months. Six reached complete remission (proteinuria under 0.3 g/day with stable serum creatinine) with intensive control of their lipid profile (normalized serum apoE and triglycerides under 100 mg/dl). Eight reached partial remission. At 3 years of follow-up, patients treated with fenofibrate had superior survival and stable renal function. Thus, fenofibrate can induce lipoprotein glomerulopathy remission and the fibrate effects depend on the degree of lipid control and baseline proteinuria. Moreover, normalization of serum apoE and triglycerides can be used to judge the efficacy of lipid-lowering treatment.