Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic kidney disease worldwide and an important cause of chronic kidney disease. Multiple experimental studies have highlighted the role of increased mammalian target of rapamycin complex 1 (mTORC1) and reduced AMP-activated protein kinase (AMPK) signaling in modulating cyst growth in ADPKD. Notably, mTORC1 and AMPK are two diametrically opposing sensors of energy metabolism which regulate cell growth and proliferation. Although pharmacological mTORC1 inhibition was highly effective in experimental studies of ADPKD, clinical trials of mTORC1 inhibitors showed a lack of efficacy with low-dose treatment and poor tolerability with high-dose treatment. Therapeutic AMPK activation has been shown to attenuate cystic kidney disease severity in Pkd1 mutant animal models by improving mitochondrial biogenesis and reducing tissue inflammation. This review summarizes the current knowledge on the function of AMPK as a regulator of cellular energy metabolism and how AMPK activation by pharmacological and non-pharmacological means can potentially be exploited to treat ADPKD in the clinical settings.

常染色体显性多囊肾病（ADPKD）是全球最常见的单基因肾病，也是慢性肾病的重要病因。多项实验研究强调了哺乳动物雷帕霉素复合物 1 (mTORC1) 靶标增加和 AMP 活化蛋白激酶 (AMPK) 信号减少在调节 ADPKD 囊肿生长中的作用。值得注意的是，mTORC1 和 AMPK 是两个截然相反的能量代谢传感器，可调节细胞生长和增殖。尽管药理学 mTORC1 抑制在 ADPKD 的实验研究中非常有效，但 mTORC1 抑制剂的临床试验表明，低剂量治疗缺乏疗效，高剂量治疗耐受性差。已显示治疗性 AMPK 激活可减轻 Pkd1 中囊性肾病的严重程度通过改善线粒体生物发生和减少组织炎症来构建突变动物模型。本综述总结了目前关于 AMPK 作为细胞能量代谢调节剂的功能的知识，以及如何利用药理学和非药理学手段激活 AMPK 来治疗临床环境中的 ADPKD。