Autosomal recessive polycystic kidney disease: the prototype of the hepato-renal fibrocystic diseases.
Autosomal recessive polycystic kidney disease: the prototype of the hepato-renal fibrocystic diseases.
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DOI：
10.3233/pge-14092
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发表时间：
2014
影响因子：
0.4
通讯作者：
Guay-Woodford LM
中科院分区：
文献类型：
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作者：
Guay-Woodford LM
常染色体隐性遗传性多囊肾病（ARPKD）是一种严重的，典型的早期发病形式的肾囊肿疾病。ARPKD患者的护理传统上一直是儿科肾病学家管理系统性高血压和进行性肾功能不全的职责范围。然而，这种疾病有多系统的表现和全面的护理策略往往需要一个多学科的团队。在严重影响的婴儿，诊断往往是第一次怀疑产科医生时，扩大，回声肾和羊水过少检测产前超声。新生儿科医生是这些婴儿的护理中心，他们可能因肺发育不全和肾脏大面积肿大而呼吸困难。在新生儿存活者中，一部分ARPKD患者具有临床显著的先天性肝纤维化，这可能导致门静脉高压，需要儿科肝病学家密切监测。可能寻求外科会诊，以获得先发制人的肾切除术，以减轻肿块效应，放置透析通路，外科分流手术，以及肾脏和/或肝脏移植。最近的数据表明，ARPKD儿童可能有神经认知功能障碍的风险，可能需要神经心理学转诊。除了这些发病率，ARPKD患者的家庭还面临着对受影响儿童进行基因检测，对无症状兄弟姐妹进行检测或考虑未来怀孕的植入前基因诊断的决定。这些问题需要遗传咨询师、遗传学家和生殖内分泌学家的投入。因此，ARPKD的管理需要多个专科医生以及普通儿科医生参与复杂的护理网络。在这篇综述中，我们讨论了这种疾病的遗传学，并提供了相关的病理生物学的概述;概述了ARPKD的临床表现和器官特异性并发症的管理频谱;讨论了其他疾病，涉及基因编码的纤毛相关蛋白，可以在临床上模仿ARPKD;审查可用于临床前研究的动物模型;最后，考虑潜在的靶向治疗的未来方向。
Autosomal recessive polycystic kidney disease (ARPKD) is a severe, typically early onset form of renal cystic disease. The care of ARPKD patients has traditionally been the purview of pediatric nephrologists for management of systemic hypertension and progressive renal insufficiency. However, the disease has multisystem manifestations and a comprehensive care strategy frequently requires a multidisciplinary team. In severely affected infants, the diagnosis often is first suspected by obstetricians when enlarged, echogenic kidneys and oligohydramnios are detected on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. Among neonatal survivors, a subset of ARPKD patients has clinically significant congenital hepatic fibrosis, which can lead to portal hypertension, requiring close monitoring by pediatric hepatologists. Surgical consultation may be sought to access pre-emptive nephrectomy to relieve mass effect, placement of dialysis access, surgical shunting procedures, and kidney and/or liver transplantation. Recent data suggest that children with ARPKD may be at risk of neurocognitive dysfunction, and may require neuropsychological referral. In addition to these morbidities, families of patients with ARPKD face decisions regarding genetic testing of affected children, testing of asymptomatic siblings, or consideration of preimplantation genetic diagnosis for future pregnancies. These issues require the input of genetic counselors, geneticists, and reproductive endocrinologists. As a result, the management of ARPKD requires the involvement of multiple subspecialists, as well as the general pediatrician, in a complex care network. In this review, we discuss the genetics of this disorder and provide an overview of the associated pathobiology; outline the spectrum of clinical manifestations of ARPKD and the management of organ-specific complications; discuss other disorders that involve genes encoding cilia-associated proteins that can clinically mimic ARPKD; review the animal models available for preclinical studies; and finally, consider future directions for potential targeted therapies.