Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Cardiovasc Drugs Ther. 2020 Jun;34(3):311-321. doi: 10.1007/s10557-020-06954-6.
The use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) is currently expanding to cardiovascular risk reduction in non-diabetic subjects, but renal (side-)effects are less well studied in this setting.
Male non-diabetic Sprague Dawley rats underwent permanent coronary artery ligation to induce MI, or sham surgery. Rats received chow containing empagliflozin (EMPA) (30 mg/kg/day) or control chow. Renal function and electrolyte balance were measured in metabolic cages. Histological and molecular markers of kidney injury, parameters of phosphate homeostasis and bone resorption were also assessed.
EMPA resulted in a twofold increase in diuresis, without evidence for plasma volume contraction or impediments in renal function in both sham and MI animals. EMPA increased plasma magnesium levels, while the levels of glucose and other major electrolytes were comparable among the groups. Urinary protein excretion was similar in all treatment groups and no histomorphological alterations were identified in the kidney. Accordingly, molecular markers for cellular injury, fibrosis, inflammation and oxidative stress in renal tissue were comparable between groups. EMPA resulted in a slight increase in circulating phosphate and PTH levels without activating FGF23-Klotho axis in the kidney and bone mineral resorption, measured with CTX-1, was not increased.
EMPA exerts profound diuretic effects without compromising renal structure and function or causing significant electrolyte imbalance in a non-diabetic setting. The slight increase in circulating phosphate and PTH after EMPA treatment was not associated with evidence for increased bone mineral resorption suggesting that EMPA does not affect bone health.
钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）的应用目前正在扩展到非糖尿病患者的心血管风险降低，但在这种情况下，肾脏（副作用）的研究较少。
雄性非糖尿病 Sprague Dawley 大鼠接受永久性冠状动脉结扎以诱导 MI，或假手术。大鼠给予含有恩格列净（EMPA）（30mg/kg/天）的饮食或对照饮食。在代谢笼中测量肾功能和电解质平衡。还评估了肾脏损伤的组织学和分子标志物、磷酸盐稳态和骨吸收的参数。
EMPA 导致尿量增加一倍，在 sham 和 MI 动物中均没有证据表明血浆体积收缩或肾功能受损。EMPA 增加了血浆镁水平，而葡萄糖和其他主要电解质的水平在各组之间相似。所有治疗组的尿蛋白排泄量相似，肾脏未发现组织形态学改变。因此，肾脏组织中细胞损伤、纤维化、炎症和氧化应激的分子标志物在各组之间相似。EMPA 导致循环磷酸盐和 PTH 水平略有升高，但不会激活肾脏和骨中的 FGF23-Klotho 轴以及骨矿物质吸收（通过 CTX-1 测量）增加。
EMPA 在非糖尿病环境中产生明显的利尿作用，而不会损害肾脏结构和功能或导致严重的电解质失衡。EMPA 治疗后循环磷酸盐和 PTH 的轻微增加与骨矿物质吸收增加的证据无关，表明 EMPA 不会影响骨骼健康。
