Metformin: the updated protective property in kidney disease

Abstract

With an aging population, the burden of kidney disease gradually occupies more and more medical resources. Between 2013 and 2016, chronic kidney disease (CKD) was reported in 14.8% of the United States (US) general adult population. As of December 31, 2016, there are 2,160.7 patients with end stage renal disease (ESRD) per 1,000,000 US citizens, according to the US Renal Data System's latest Annual Data Report [1]. Therefore, there is an urgent demand for effective drugs to delay kidney impairment.Beyond its hypoglycemic action, metformin has pleiotropic protective effects in various disease models, including polycystic ovary syndrome [2], cancer [3], neurological disorders [4], and kidney disease [5]. In particular, emerging evidence has demonstrated potential protective effects of metformin on acute kidney injury (AKI), CKD, diabetic kidney disease (DKD), autosomal dominant (adult) polycystic kidney disease (ADPKD), lupus nephritis (LN), renal neoplasm, and kidney transplantation [6][7][8][9][10][11][12].Metformin protects the kidneys mainly via AMPactivated protein kinase (AMPK) signaling and AMPKindependent pathways. AMPK is a well-known energy and nutrient sensor, which regulates the switch from anabolic to catabolic metabolism to control energy homeostasis [13]. Many kidney diseases are intertwined with abnormal metabolic status, such as hyperglycemia, hyperlipidemia, and hyperuricemia. And many studies has explored the relationship between depressed AMPK activity and kidney disease [14][15][16], revealing that the AMPK agonist metformin exerts protective actions in a variety of kidney disease models, including those induced by hyperglycemia, advanced glycation end products (AGEs), proteinuria, and high fatty www.aging-us.com

Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside

“…However, its effects are likely pleiotropic because metformin acts on the metabolism and inflammation via both adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms, leading to kidney protection. Potential uses of metformin in kidney disease have been extensively reviewed elsewhere [ 15 , 16 , 17 ].…”

Metformin Protects against Podocyte Injury in Diabetic Kidney Disease

“…As in other tissues, also in the kidney metformin acts via both AMPK-dependent and -independent pathways as described in the following paragraphs, in which I will concentrate on the effects of metformin in podocytes. For comprehensive reviews covering the effects of metformin in the kidney beyond podocytes, see the following recent review articles [ 93 , 94 , 95 , 96 , 97 ]. The mechanisms of action of metformin in different tissues are reviewed in [ 98 ].…”

“…Metformin also ameliorates the senescence of renal tubular cells in culture and in diabetic db/db mice by up-regulating miR-130a-3p and down-regulating STAT3, a target gene of miR-130a-3p involved in the pathogenesis of DKD [ 136 ]. For recent reviews on the beneficial effects of metformin in the kidney at large, the readers are referred to [ 93 , 94 , 95 , 96 , 97 ].…”

Metformin improves renal injury of MRL/lpr lupus-prone mice via the AMPK/STAT3 pathway

“…Growing evidence has revealed that metformin has antitumour, antiageing, cardiovascular protective, anti-inflammatory and immune regulatory effects though AMP-activated protein kinase (AMPK)-dependent and independent pathways. 9 Metformin also protects against renal inflammation and fibrosis in experimental models. 10–12 A registered clinical trial recently analysed metformin as an SLE treatment.…”