Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium.
Int J Mol Sci. 2018 Dec 21;20(1):42. doi: 10.3390/ijms20010042.
Over the past decades metformin has been the optimal first-line treatment for type 2 diabetes mellitus (T2DM). Only in the last few years, it has become increasingly clear that metformin exerts benign pleiotropic actions beyond its prescribed use and ongoing investigations focus on a putative beneficial impact of metformin on the kidney. Both acute kidney injury (AKI) and chronic kidney disease (CKD), two major renal health issues, often result in the need for renal replacement therapy (dialysis or transplantation) with a high socio-economic impact for the patients. Unfortunately, to date, effective treatment directly targeting the kidney is lacking. Metformin has been shown to exert beneficial effects on the kidney in various clinical trials and experimental studies performed in divergent rodent models representing different types of renal diseases going from AKI to CKD. Despite growing evidence on metformin as a candidate drug for renal diseases, in-depth research is imperative to unravel the molecular signaling pathways responsible for metformin's renoprotective actions. This review will discuss the current state-of-the-art literature on clinical and preclinical data, and put forward potential cellular mechanisms and molecular pathways by which metformin ameliorates AKI/CKD.
在过去的几十年中，二甲双胍一直是治疗 2 型糖尿病（T2DM）的最佳一线治疗药物。直到最近几年，二甲双胍除了规定用途之外还具有良性的多效作用，这一点才越来越明显，并且正在进行的研究集中在二甲双胍对肾脏的潜在有益影响上。急性肾损伤（AKI）和慢性肾脏病（CKD）是两个主要的肾脏健康问题，通常需要进行肾脏替代治疗（透析或移植），这对患者的社会经济影响很大。不幸的是，迄今为止，缺乏直接针对肾脏的有效治疗方法。在各种临床试验和实验研究中，二甲双胍已被证明对肾脏具有有益作用，这些研究在不同的啮齿动物模型中进行，这些模型代表了从 AKI 到 CKD 等不同类型的肾脏疾病。尽管有越来越多的证据表明二甲双胍是肾脏疾病的候选药物，但深入研究对于揭示二甲双胍的肾脏保护作用的分子信号通路至关重要。这篇综述将讨论关于临床和临床前数据的最新文献，并提出二甲双胍改善 AKI/CKD 的潜在细胞机制和分子途径。
