Dapagliflozin for the treatment of chronic kidney disease
Dapagliflozin for the treatment of chronic kidney disease
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DOI：
10.1080/17446651.2022.2099373
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发表时间：
2022-07-15
影响因子：
3.2
通讯作者：
Nangaku, Masaomi
中科院分区：
文献类型：
--
作者：
Kurata, Yu;Nangaku, Masaomi
简介：钠依赖性葡萄糖协同转运蛋白2（SGLT 2）是一种在近端肾小管细胞上表达的葡萄糖转运蛋白，在近端肾小管细胞中它从肾小球滤液中重吸收葡萄糖。SGLT 2抑制剂（SGLT 2 is）最初是作为一种抗糖尿病药物开发的，最近因其具有心肾保护作用而引起了广泛关注。在SGLT 2 is中，达格列净是第一个在糖尿病患者和非糖尿病患者中证明具有肾脏保护作用的药物，并已被批准用于慢性肾脏病（CKD）治疗。涵盖领域：本综述涵盖了达格列净的药理学特征、临床疗效和安全性，包括与其他SGLT 2 is的比较以及风险调整策略。在DAPA-CKD中，达格列净降低了主要结局（？50%估计肾小球滤过率[eGFR]下降、终末期肾病[ESKD]或肾或心血管[CV]死亡）。这种有益效果在预先指定的亚组中是一致的，包括那些基于糖尿病的亚组。达格列净还使CV复合结局和全因死亡分别降低了29%和31%。尽管已报告酮症酸中毒和血容量不足等不良事件的风险增加，但预计达格列净的稳健肾脏和CV获益超过潜在风险。SGLT 2 is（包括达格列净）将构成CKD治疗的主要药物。
Introduction: Sodium-dependent glucose cotransporter 2 (SGLT2) is a glucose transporter expressed on the proximal tubular cells, where it reabsorbs glucose from the glomerular filtrate. SGLT2 inhibitors (SGLT2is), initially developed as an antidiabetic drug, have recently attracted considerable attention because they have cardiorenal protective effects. Among SGLT2is, dapagliflozin was the first to demonstrate the renoprotective effect in patients with and without diabetes and has been approved for chronic kidney disease (CKD) treatment.Areas covered: This review covers the pharmacological characteristics and the clinical efficacy and safety profiles of dapagliflozin, including comparison with other SGLT2is and risk modification strategies.Expert opinion: In DAPA-CKD, dapagliflozin reduced the primary outcome (?.50% estimated glomerular filtration rate [eGFR] decline, end-stage kidney disease [ESKD], or renal or cardiovascular [CV] death) by 39% in CKD patients. This beneficial effect was consistent across prespecified subgroups, including those based on the presence of diabetes. Dapagliflozin also decreased the CV composite outcome and all-cause death by 29% and 31%, respectively. Although an increased risk of adverse events such as ketoacidosis and volume depletion has been reported, the robust renal and CV benefits of dapagliflozin are expected to outweigh potential risks. SGLT2is, including dapagliflozin, will constitute the mainstay of CKD treatment.