Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China.
Aging (Albany NY). 2020 May 1;12(9):8742-8759. doi: 10.18632/aging.103095.
Metformin is a frontline hypoglycemic agent, which is mainly prescribed to manage type 2 diabetes mellitus with obesity. Emerging evidence suggests that metformin also exerts protective effects against various kidney diseases. Some postulate that kidney disease is actually a metabolic disease, accompanied by nonresolving pathophysiologic pathways controlling oxidative stress, endoplasmic reticulum stress, inflammation, lipotoxicity, fibrosis, and senescence, as well as insufficient host defense mechanisms such as AMP-activated protein kinase (AMPK) signaling and autophagy. Metformin may interfere with these pathways by orchestrating AMPK signaling and AMPK-independent pathways to protect the kidneys from injury. Furthermore, the United States Food and Drug Administration declared metformin is safe for patients with mild or moderate kidney impairment in 2016, assuaging some conservative attitudes about metformin management in patients with renal insufficiency and broadening the scope of research on the renal protective effects of metformin. This review focuses on the molecular mechanisms by which metformin imparts renal protection and its potential in the treatment of various kidney diseases.
二甲双胍是一种一线降血糖药物，主要用于治疗肥胖的 2 型糖尿病。新出现的证据表明，二甲双胍对各种肾脏疾病也具有保护作用。有人推测，肾脏疾病实际上是一种代谢疾病，伴有未解决的病理生理途径，这些途径控制着氧化应激、内质网应激、炎症、脂毒性、纤维化和衰老，以及宿主防御机制不足，如 AMP 激活的蛋白激酶 (AMPK) 信号和自噬。二甲双胍可能通过协调 AMPK 信号和 AMPK 非依赖性途径来干扰这些途径，从而保护肾脏免受损伤。此外，美国食品和药物管理局于 2016 年宣布二甲双胍对轻度或中度肾功能损害的患者是安全的，这减轻了一些关于肾功能不全患者使用二甲双胍管理的保守态度，并拓宽了二甲双胍对肾脏保护作用的研究范围。本综述重点介绍了二甲双胍发挥肾脏保护作用的分子机制及其在治疗各种肾脏疾病中的潜力。
