van Gastel Maatje D A, Torres Vicente E
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Ann Nutr Metab. 2017;70 Suppl 1:43-50. doi: 10.1159/000463063. Epub 2017 Jun 15.
Vasopressin, also known as arginine vasopressin or antidiuretic hormone, plays a pivotal role in maintaining body homeostasis. Increased vasopressin concentrations, measured by its surrogate copeptin, have been associated with disease severity as well as disease progression in polycystic kidney disease (PKD), and in experimental studies vasopressin has been shown to directly regulate cyst growth. Blocking vasopressin effects on the kidney via the vasopressin V2-receptor and lower circulating vasopressin concentration are potential treatment opportunities that have been the subject of study in PKD in recent years. Treatment with vasopressin V2-receptor antagonist tolvaptan has been shown to inhibit disease progression in experimental studies, as well as in a large randomized controlled trial involving 1,445 patients with autosomal dominant PKD, lowering total kidney volume growth from 5.5 to 2.8%, and the slope of the reciprocal of the serum creatinine level from -3.81 to -2.61 mg per mL-1/year. Alternatively, lowering circulating vasopressin could delay disease progression. Vasopressin is secreted in response to an increased plasma osmolality, which in turn is caused by a low fluid or high osmolar intake. Other lifestyle factors, like smoking, increase vasopressin concentration. Here, we provide a comprehensive review of the physiology as well as pathophysiology of vasopressin in PKD, the promising effects of tolvaptan treatment, and potential synergistic or additive treatments in combination with tolvaptan. In this study, we also review current evidence regarding the effect of influencing disease progression in PKD by lifestyle changes, especially by fluid intake.
血管加压素，也称为精氨酸血管加压素或抗利尿激素，在维持身体内环境稳定方面起着关键作用。通过其替代物 copeptin 测量的血管加压素浓度升高，与多囊肾病（PKD）的疾病严重程度以及疾病进展相关，并且在实验研究中已表明血管加压素可直接调节囊肿生长。通过血管加压素 V2 受体阻断血管加压素对肾脏的作用以及降低循环中的血管加压素浓度是近年来 PKD 研究的潜在治疗机会。血管加压素 V2 受体拮抗剂托伐普坦治疗已在实验研究以及一项涉及 1445 例常染色体显性 PKD 患者的大型随机对照试验中显示可抑制疾病进展，使总肾体积生长从 5.5%降至 2.8%，血清肌酐水平倒数的斜率从 -3.81 降至 -2.61 mg/mL-1/年。或者，降低循环中的血管加压素可延缓疾病进展。血管加压素是对血浆渗透压升高作出反应而分泌的，而血浆渗透压升高又是由低液体摄入或高渗透压摄入引起的。其他生活方式因素，如吸烟，会增加血管加压素浓度。在此，我们对 PKD 中血管加压素的生理学以及病理生理学、托伐普坦治疗的有前景的效果以及与托伐普坦联合使用的潜在协同或相加治疗进行全面综述。在本研究中，我们还综述了关于通过生活方式改变，特别是通过液体摄入来影响 PKD 疾病进展的效果的当前证据。
