Del Vecchio Lucia, Beretta Angelo, Jovane Carlo, Peiti Silvia, Genovesi Simonetta
Department of Nephrology and Dialysis, Sant'Anna Hospital, ASST Lariana, Como, Italy.
Internal Medicine Unit, Valduce Hospital, 22100, Como, Italy.
Drugs. 2021 Sep;81(13):1491-1511. doi: 10.1007/s40265-021-01573-3. Epub 2021 Aug 7.
In recent years, inhibitors of the sodium-glucose co-transporter 2 (SGLT2 inhibitors) have been shown to have significant protective effects on the kidney and the cardiovascular system in patients with diabetes. This effect is also manifested in chronic kidney disease (CKD) patients and is minimally due to improved glycaemic control. Starting from these positive findings, SGLT2 inhibitors have also been tested in patients with non-diabetic CKD or heart failure with reduced ejection fraction. Recently, the DAPA-CKD trial showed a significantly lower risk of CKD progression or death from renal or cardiovascular causes in a mixed population of patients with diabetic and non-diabetic CKD receiving dapagliflozin in comparison with placebo. In patients with heart failure and reduced ejection fraction, two trials (EMPEROR-Reduced and DAPA-HF) also found a significantly lower risk of reaching the secondary renal endpoint in those treated with an SGLT2 inhibitor in comparison with placebo. This also applied to patients with CKD. Apart from their direct mechanism of action, SGLT2 inhibitors have additional effects that could be of particular interest for patients with non-diabetic CKD. Among these, SGLT2 inhibitors reduce blood pressure and serum acid uric levels and can increase hemoglobin levels. Some safety issues should be further explored in the CKD population. SGLT2 inhibitors can minimally increase potassium levels, but this has not been shown by the CREDENCE trial. They also increase magnesium and phosphate reabsorption. These effects could become more significant in patients with advanced CKD and will need monitoring when these agents are used more extensively in the CKD population. Conversely, they do not seem to increase the risk of acute kidney injury.
近年来，钠-葡萄糖协同转运蛋白2抑制剂（SGLT2抑制剂）已被证明对糖尿病患者的肾脏和心血管系统具有显著的保护作用。这种作用在慢性肾脏病（CKD）患者中也有体现，且极少归因于血糖控制的改善。基于这些积极的研究结果，SGLT2抑制剂也在非糖尿病CKD患者或射血分数降低的心力衰竭患者中进行了试验。最近，DAPA-CKD试验表明，在接受达格列净治疗的糖尿病和非糖尿病CKD混合患者群体中，与安慰剂相比，CKD进展或因肾脏或心血管原因死亡的风险显著降低。在射血分数降低的心力衰竭患者中，两项试验（EMPEROR-Reduced和DAPA-HF）也发现，与安慰剂相比，接受SGLT2抑制剂治疗的患者达到次要肾脏终点的风险显著降低。这同样适用于CKD患者。除了其直接作用机制外，SGLT2抑制剂还有其他一些作用，对于非糖尿病CKD患者可能特别有意义。其中，SGLT2抑制剂可降低血压和血清尿酸水平，并能提高血红蛋白水平。一些安全问题在CKD人群中应进一步探讨。SGLT2抑制剂可轻微升高血钾水平，但CREDENCE试验未显示出这一点。它们还会增加镁和磷的重吸收。在晚期CKD患者中，这些作用可能会更加显著，当这些药物在CKD人群中更广泛使用时，需要进行监测。相反，它们似乎不会增加急性肾损伤的风险。
