Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Diseases of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
Front Immunol. 2023 Sep 21;14:1213473. doi: 10.3389/fimmu.2023.1213473. eCollection 2023.
Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.
糖尿病肾病（DKD）是一种慢性炎症性疾病，影响大约 20-40%的糖尿病患者。钠-葡萄糖共转运蛋白 2（SGLT-2）抑制剂作为新型降糖药物，已在 DKD 患者中显示出显著的心肾保护作用。最初，人们认为 SGLT-2 抑制剂的疗效随着估算肾小球滤过率（eGFR）的降低而下降，这导致它们在 G1-G3 期的 DKD 患者中优先使用。然而，DAPA-CKD 和 EMPA-KIDNEY 研究的最新发现表明，SGLT-2 抑制剂在 G4 期 DKD 患者中也具有同样有益的心肾作用，尽管其背后的机制尚不清楚。在这项全面分析中，我们系统地综述了 SGLT-2 抑制剂的作用机制、潜在的肾脏保护机制以及 SGLT-2 抑制剂在肾脏疾病中的治疗效果和安全性，特别关注 G4 期 DKD。深入了解 SGLT-2 抑制剂的肾脏保护作用及其潜在机制，对于成功利用这些抑制剂治疗各种肾脏疾病具有重要意义。
