Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and is one of the most frequent genetic causes for kidney failure (KF) in children and adolescents. Over 20 genes cause NPHP and over 90 genes contribute to renal ciliopathies often involving multiple organs. About 15–20% of NPHP patients have additional extrarenal symptoms affecting other organs than the kidneys. The involvement of additional organ systems in syndromic forms of NPHP is explained by shared expression of most NPHP gene products in centrosomes and primary cilia, a sensory organelle present in most mammalian cells. This finding resulted in the classification of NPHP as a ciliopathy. If extrarenal symptoms are present in addition to NPHP, these disorders are defined as NPHP-related ciliopathies (NPHP-RC) and can involve the retina (e.g., with Senior-Løken syndrome), CNS (central nervous system) (e.g., with Joubert syndrome), liver (e.g., Boichis and Arima syndromes), or bone (e.g., Mainzer-Saldino and Sensenbrenner syndromes). This review focuses on the pathological findings and the recent genetic advances in NPHP and NPHP-RC. Different mechanisms and signaling pathways are involved in NPHP ranging from planar cell polarity, sonic hedgehog signaling (Shh), DNA damage response pathway, Hippo, mTOR, and cAMP signaling. A number of therapeutic interventions appear to be promising, ranging from vasopressin receptor 2 antagonists such as tolvaptan, cyclin-dependent kinase inhibitors such as roscovitine, Hh agonists such as purmorphamine, and mTOR inhibitors such as rapamycin.

肾痨 (NPHP) 是一种常染色体隐性遗传性囊性肾病，是儿童和青少年肾衰竭 (KF) 最常见的遗传原因之一。超过 20 个基因会导致 NPHP，超过 90 个基因会导致肾纤毛病（通常涉及多个器官）。大约 15-20% 的 NPHP 患者有额外的肾外症状，影响肾脏以外的其他器官。NPHP 综合征形式中其他器官系统的参与可以通过大多数NPHP基因产物在中心体和初级纤毛（大多数哺乳动物细胞中存在的感觉细胞器）中的共同表达来解释。这一发现导致 NPHP 被归类为纤毛病。如果除了 NPHP 之外还存在肾外症状，这些疾病被定义为 NPHP 相关纤毛病 (NPHP-RC)，并且可能累及视网膜（例如，Senior-Løken 综合征）、CNS（中枢神经系统）（例如，Joubert 综合征）综合征）、肝脏（例如，Boichis 和 Arima 综合征）或骨骼（例如，Mainzer-Saldino 和 Sensenbrenner 综合征）。本文重点介绍 NPHP 和 NPHP-RC 的病理学发现和最新遗传学进展。NPHP 涉及不同的机制和信号传导途径，包括平面细胞极性、声波刺猬信号传导 (Shh)、DNA 损伤反应途径、Hippo、mTOR 和 cAMP 信号传导。许多治疗干预措施似乎都有希望，包括托伐普坦等加压素受体 2 拮抗剂、罗可维汀等细胞周期蛋白依赖性激酶抑制剂、嘌吗啡胺等 Hh 激动剂和雷帕霉素等 mTOR 抑制剂。