The Clinical Manifestation and Management of Autosomal Dominant Polycystic Kidney Disease in China
The Clinical Manifestation and Management of Autosomal Dominant Polycystic Kidney Disease in China
复制标题
DOI：
10.1159/000449030
复制
发表时间：
2016-10
期刊：
影响因子：
3.7
通讯作者：
C. Xue;Chen Zhou;Ming Wu;C. Mei
中科院分区：
文献类型：
--
作者：
C. Xue;Chen Zhou;Ming Wu;C. Mei
背景：常染色体显性多囊肾病（ADPKD）是最常见的单基因遗传性肾脏疾病，其特征是肾囊肿进行性扩大。全世界发病率为1-2‰。两个基因（PKD1和PKD2）的突变会导致ADPKD。目前，中国还没有针对ADPKD患者的药物治疗。综述了中国ADPKD的临床表现、基因诊断、危险因素及治疗进展。在中国ADPKD患者中，总肾容量（TKV）的增加与肾功能的下降具有年龄依赖性。ADPKD在男性中比女性更严重。近二十年来，分子诊断取得了很大的进展。肾病学家通过聚合酶链反应，在中国ADPKD患者中发现了许多新的PKD突变，然后在2000年代通过液相色谱，最近通过下一代测序。ADPKD进展的主要预测因素是年龄、PKD基因型、性别、估计肾小球滤过率（eGFR）和TKV。在ADPKD的治疗方面，靶向mTOR和cAMP的抑制剂是临床试验的重点。雷公藤甲素已在中国的临床试验中用于治疗ADPKD患者。与安慰剂相比，雷公藤甲素显著保护ADPKD患者的eGFR。关键信息：ADPKD在中国影响约150万人。除PKD1和PKD2外，在中国人中未发现另一个PKD基因。中国ADPKD患者颅内动脉瘤患病率为12.4%。中国ADPKD患者eGFR下降的预测因素有TKV、蛋白尿、高血压史和年龄。除雷公藤甲素外，中国ADPKD临床试验的治疗策略与西方相似。来自东西方的事实：(1)在全球范围内，ADPKD是通过超声检测肾脏肿大和囊肿来诊断的。最近通过下一代测序对中国和西方ADPKD患者PKD1和PKD2基因变异的分析可能会导致可靠的基因检测的发展。(2)除了改变生活方式（低盐饮食、充足的液体摄入和不吸烟），控制血压是肾脏疾病-改善全球预后（KDIGO）推荐的ADPKD患者的主要非特异性治疗方法。根据慢性肾脏疾病的严重程度和患者的年龄，血压目标应该有多低以及实现这一目标的方法仍然是一个悬而未决的问题。在中国最近的一项研究中，诊断性吸针和腹腔镜去顶手术成功地改善了感染、疼痛和高血压。腹膜透析是大多数中国ADPKD终末期肾病患者可行的治疗方法。在大多数西方中心，选择无禁忌症的患者进行腹膜透析。肾移植联合双侧肾切除术在缓解中国ADPKD患者高血压和感染方面是成功的。在西方国家，为了降低风险，首选在肾切除术后进行序贯手术干预并进行肾移植，或者相反。(3)加压素2受体拮抗剂托伐普坦在欧洲、加拿大、日本和韩国被批准用于减缓ADPKD患者肾脏疾病的进展。Tolvaptan尚未在美国或中国获得批准。mTOR通路靶向药物目前正在评估中：在西方和日本的一组ADPKD患者中，mTOR抑制剂可以减缓肾脏总容量的增加。西方的研究以及中国正在进行的一项研究未能显示雷帕霉素的益处。在意大利进行的一项研究表明，生长抑素类似物奥曲肽对ADPKD患者有保护作用。西方和中国的研究表明，雷公藤的活性物质雷公藤内酯对预防ADPKD患者病情恶化具有潜在的有益作用。
Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic hereditary kidney disease characterized by progressive enlargement of renal cysts. The incidence is 1-2‰ worldwide. Mutations in two genes (PKD1 and PKD2) cause ADPKD. Currently, there is no pharmaceutical treatment available for ADPKD patients in China. Summary: This review focused on advances in clinical manifestation, gene diagnosis, risk factors, and management of ADPKD in China. There is an age-dependent increase in total kidney volume (TKV) and decrease in renal function in Chinese ADPKD patients. ADPKD is more severe in males than in females. Great progress has been made in molecular diagnosis in the last two decades. Nephrologists found many novel PKD mutations in Chinese ADPKD patients early through polymerase chain reaction, and then through liquid chromatography in 2000s, and recently through next-generation sequencing. Major predictive factors for ADPKD progression are age, PKD genotype, sex, estimated glomerular filtration rate (eGFR), and TKV. With respect to the management of ADPKD, inhibitors targeting mTOR and cAMP are the focus of clinical trials. Triptolide has been used to treat ADPKD patients in clinical trials in China. Triptolide significantly protected eGFR of ADPKD patients compared with placebo. Key Messages: ADPKD affects about 1.5 million people in China. An additional PKD gene besides PKD1 and PKD2 was not found in the Chinese. The prevalence of intracranial aneurysm in Chinese ADPKD patients was 12.4%. The predictive factors for eGFR decrease in Chinese ADPKD patients are TKV, proteinuria, history of hypertension, and age. The treatment strategies in clinical trials for ADPKD patients in China are similar to those in the West except for triptolide. Facts from East and West: (1) ADPKD is diagnosed globally by ultrasound detection of kidney enlargement and presence of cysts. Recent analyses of variants of the PKD1 and PKD2 genes by next-generation sequencing in Chinese and Western ADPKD patients might lead to the development of reliable genetic tests. (2) Besides lifestyle changes (low-salt diet, sufficient fluid intake, and no smoking), blood pressure control is the primary nonspecific treatment recommended by Kidney Disease - Improving Global Outcomes (KDIGO) for ADPKD patients. How low the blood pressure target should be and what the means of achieving it are remain open questions depending on the severity of chronic kidney disease and the age of the patients. In a recent Chinese study, diagnostic needle aspiration and laparoscopic unroofing surgery successfully improved infection, pain, and hypertension. Peritoneal dialysis was found to be a feasible treatment for most Chinese ADPKD patients with end-stage renal disease. In most Western centers, patients without contraindication are selected for peritoneal dialysis. Kidney transplantation with concurrent bilateral nephrectomy was successful in relieving hypertension and infection in Chinese ADPKD patients. In Western countries, sequential surgical intervention with kidney transplantation after nephrectomy, or the other way round, is preferred in order to reduce risks. (3) The vasopressin 2 receptor antagonist tolvaptan was approved in Europe, Canada, Japan, and Korea to slow down progression of kidney disease in ADPKD patients. Tolvaptan is not yet approved in the USA or in China. mTOR pathway-targeting drugs are currently under evaluation: mTOR inhibitors could slow down the increase in total kidney volume in a cohort of Western and Japanese ADPKD patients. Western studies as well as an ongoing study in China failed to show benefit from rapamycin. A study performed in Italy indicates protective effects of the somatostatin analog octreotide in ADPKD patients. Western and Chinese studies revealed a potential beneficial effect of triptolide, the active substance of the traditional Chinese medicine Tripterygium wilfordii (Lei Gong Teng) to prevent worsening in ADPKD patients.