INSERM, U574, Hôpital Necker Enfants Malades, Faculté de Médecine Paris Descartes, Université Paris Descartes, Paris, France.
Kidney Int. 2010 Mar;77(5):400-6. doi: 10.1038/ki.2009.423. Epub 2009 Nov 18.
Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence. At birth, blood pressure is dramatically low and perinatal death occurs in most cases. Skull ossification defects are frequently associated with RTD. The disease is genetically heterogeneous and linked to mutations in the genes encoding any of the components of the renin-angiotensin system (RAS). An intense stimulation of renin production is noted in the kidneys of patients with mutations in the genes encoding angiotensinogen, angiotensin-converting enzyme, or AT1 receptor, whereas absence or increased renin production is associated with REN defects depending on the type of mutation. The severity of the disease underlines the importance of a functional RAS in the maintenance of blood pressure and renal blood flow during fetal life. The absence or poor development of proximal tubules, as well as renal vascular changes, may be attributable to renal hypoperfusion rather than to a morphogenic property of the RAS. The less severe phenotype in mice devoid of RAS may be linked to differences between mice and humans in the time of nephrogenesis and maturation of the RAS. The identification of the disease on the basis of precise clinical and histological analyses and the characterization of the genetic defects allow genetic counseling and early prenatal diagnosis.
常染色体隐性遗传性肾小管发育不良（RTD）是一种严重的肾小管发育障碍，其特征为早期发病和持续性胎儿无尿导致羊水过少和波特序列。出生时，血压显著降低，大多数情况下会发生围产期死亡。颅骨骨化缺陷常与 RTD 相关。该疾病具有遗传异质性，与编码肾素-血管紧张素系统（RAS）任何成分的基因突变有关。在编码血管紧张素原、血管紧张素转换酶或 AT1 受体的基因突变患者的肾脏中，肾素的产生受到强烈刺激，而 REN 缺陷则与肾素的缺乏或增加有关，具体取决于突变的类型。疾病的严重程度强调了功能性 RAS 在维持胎儿期血压和肾血流量方面的重要性。近端小管的缺失或发育不良以及肾血管变化可能归因于肾灌注不足，而不是 RAS 的形态发生特性。缺乏 RAS 的小鼠表型较轻可能与啮齿动物和人类在肾发生和 RAS 成熟时间上的差异有关。基于精确的临床和组织学分析以及遗传缺陷的特征，可以进行疾病的鉴定和遗传咨询以及早期产前诊断。
