Laboratory of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
Department of Nephrology, University Hospitals Brussel, Brussel, Belgium.
Pediatr Nephrol. 2018 Mar;33(3):395-408. doi: 10.1007/s00467-017-3672-x. Epub 2017 Apr 28.
Polycystic kidney disease (PKD) encompasses a group of genetic disorders that are common causes of renal failure. The two classic forms of PKD are autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD). Despite their clinical differences, ARPKD and ADPKD share many similarities. Altered intracellular Ca and increased cyclic adenosine monophosphate (cAMP) concentrations have repetitively been described as central anomalies that may alter signaling pathways leading to cyst formation. The vasopressin V2 receptor (V2R) antagonist tolvaptan lowers cAMP in cystic tissues and slows renal cystic progression and kidney function decline when given over 3 years in adult ADPKD patients. Tolvaptan is currently approved for the treatment of rapidly progressive disease in adult ADPKD patients. On the occasion of the recent initiation of a clinical trial with tolvaptan in pediatric ADPKD patients, we aim to describe the most important aspects in the literature regarding the AVP-cAMP axis and the clinical use of tolvaptan in PKD.
多囊肾病 (PKD) 包括一组遗传疾病，是肾衰竭的常见原因。PKD 的两种典型形式是常染色体隐性多囊肾病 (ARPKD) 和常染色体显性多囊肾病 (ADPKD)。尽管它们在临床上存在差异，但 ARPKD 和 ADPKD 有许多相似之处。细胞内钙的改变和环腺苷酸 (cAMP) 浓度的增加被反复描述为中心异常，可能改变导致囊肿形成的信号通路。加压素 V2 受体 (V2R) 拮抗剂托伐普坦降低囊状组织中的 cAMP，并在成年 ADPKD 患者中使用 3 年以上时减缓肾脏囊肿的进展和肾功能下降。托伐普坦目前被批准用于治疗成年 ADPKD 患者的快速进展性疾病。鉴于最近在儿科 ADPKD 患者中开始进行托伐普坦的临床试验，我们旨在描述文献中关于 AVP-cAMP 轴和托伐普坦在 PKD 中的临床应用的最重要方面。
