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钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂的肾脏保护作用:超越葡萄糖重吸收抑制

Renoprotective Effects of SGLT2 Inhibitors: Beyond Glucose Reabsorption Inhibition.

作者信息

Tsimihodimos V, Filippatos T D, Filippas-Ntekouan S, Elisaf M

机构信息

Department of Internal Medicine, School of Medicine, University of Ioannina, 45 110 Ioannina, Greece.

出版信息

Curr Vasc Pharmacol. 2017;15(2):96-102. doi: 10.2174/1570161114666161007163426.

Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that inhibit glucose and sodium reabsorption at proximal tubules. These drugs may exhibit renoprotective properties, since they prevent the deterioration of the glomerular filtration rate and reduce the degree of albuminuria in patients with diabetes-associated kidney disease. In this review we consider the pathophysiologic mechanisms that have been recently implicated in the renoprotective properties of SGLT2 inhibitors. The beneficial effects of SGLT2 inhibitors on the conventional risk factors for kidney disease (such as blood pressure, hyperglycaemia, body weight and serum uric acid levels) may explain, at least in part, the observed renal-protecting properties of these compounds. However, it has been hypothesized that the most important mechanisms for this phenomenon include the reduction in the intraglomerular pressure, the changes in the local and systemic degree of activation of the renin-aldosterone-angiotensin system and a shift in renal fuel consumption towards more efficient energy substrates such as ketone bodies. The beneficial effects of SGLT2 inhibitors on various aspects of renal function make them an attractive choice in patients with (and possibly without) diabetes-associated renal impairment.

摘要

钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂是一类新型抗糖尿病药物,可抑制近端肾小管对葡萄糖和钠的重吸收。这些药物可能具有肾脏保护作用,因为它们可防止糖尿病相关肾病患者的肾小球滤过率恶化,并降低蛋白尿程度。在本综述中,我们探讨了近期与SGLT2抑制剂肾脏保护作用相关的病理生理机制。SGLT2抑制剂对肾病传统危险因素(如血压、高血糖、体重和血清尿酸水平)的有益作用,可能至少部分解释了这些化合物所观察到的肾脏保护特性。然而,据推测,这一现象最重要的机制包括肾小球内压力降低、肾素-醛固酮-血管紧张素系统局部和全身激活程度的变化,以及肾脏能量消耗向更高效能量底物(如酮体)的转变。SGLT2抑制剂对肾功能各个方面的有益作用,使其成为糖尿病相关肾损伤患者(可能也适用于无糖尿病相关肾损伤患者)的一个有吸引力的选择。

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