Department of Medicine, Division of Nephrology, University of Toledo College of Medicine, Toledo, OH, United States.
Front Endocrinol (Lausanne). 2021 Nov 1;12:749010. doi: 10.3389/fendo.2021.749010. eCollection 2021.
As the prevalence of diabetic kidney disease (DKD) continues to rise, so does the need for a novel therapeutic modality that can control and slow its progression to end-stage renal disease. The advent of sodium-glucose cotransporter-2 (SGLT2) inhibitors has provided a major advancement for the treatment of DKD. However, there still remains insufficient understanding of the mechanism of action and effectiveness of this drug, and as a result, its use has been very limited. Burgeoning evidence suggests that the SGLT2 inhibitors possess renal protective activities that are able to lower glycemic levels, improve blood pressure/hemodynamics, cause bodyweight loss, mitigate oxidative stress, exert anti-inflammatory and anti-fibrotic effects, reduce urinary albumin excretion, lower uric acid levels, diminish the activity of intrarenal renin-angiotensin-aldosterone system, and reduce natriuretic peptide levels. SGLT2 inhibitors have been shown to be safe and beneficial for use in patients with a GFR ≥30mL/min/1.73m, associated with a constellation of signs of metabolic reprogramming, including enhanced ketogenesis, which may be responsible for the correction of metabolic reprogramming that underlies DKD. This article aims to provide a comprehensive overview and better understanding of the SGLT2 inhibitor and its benefits as it pertains to renal pathophysiology. It summarizes our recent understanding on the mechanisms of action of SGLT2 inhibitors, discusses the effects of SGLT2 inhibitors on diabetes and DKD, and presents future research directions and therapeutic potential.
随着糖尿病肾病 (DKD) 的患病率持续上升，我们需要一种新的治疗方法来控制和减缓其向终末期肾病的进展。钠-葡萄糖共转运蛋白 2 (SGLT2) 抑制剂的出现为 DKD 的治疗提供了重大进展。然而，人们对这种药物的作用机制和疗效仍缺乏足够的了解，因此其应用非常有限。越来越多的证据表明，SGLT2 抑制剂具有肾脏保护作用，能够降低血糖水平、改善血压/血液动力学、减轻体重、减轻氧化应激、发挥抗炎和抗纤维化作用、减少尿白蛋白排泄、降低尿酸水平、降低肾内肾素-血管紧张素-醛固酮系统的活性、降低利钠肽水平。SGLT2 抑制剂已被证明在肾小球滤过率 (GFR) ≥30mL/min/1.73m 的患者中安全且有益，与一系列代谢重编程的迹象相关，包括增强酮生成，这可能是导致 DKD 潜在代谢重编程得到纠正的原因。本文旨在全面概述和更好地理解 SGLT2 抑制剂及其在肾脏病理生理学方面的益处。它总结了我们最近对 SGLT2 抑制剂作用机制的理解，讨论了 SGLT2 抑制剂对糖尿病和 DKD 的影响，并提出了未来的研究方向和治疗潜力。
