Department of Nephrology, Kindai University Faculty of Medicine, Kindai University Nara Hospital, Nara, Japan.
J Diabetes Complications. 2018 Jul;32(7):720-725. doi: 10.1016/j.jdiacomp.2018.04.011. Epub 2018 May 5.
Diabetic kidney disease (DKD) is the most frequent cause of mortality and morbidity, leading a global health burden. This review will focus on the potential therapeutic interventions using Sodium-glucose cotransporter-2 (SGLT2) inhibitors that could prevent the development and progression of DKD.
SGLT2 inhibitors have been widely used as anti-diabetic drugs. Recent clinical studies have demonstrated that these drugs, which improve glycemic control and hypertension and decrease body weight, decrease the risk of renal function impairment and heart failure in patients with type 2 diabetes. With regard to long-term clinical outcomes, the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME), the EMPA-REG Renal OUTCOME, and the CANagliflozin cardioVascular Assessment Study (CANVAS) program which have been integrated from CANVAS and CANVAS-Renal (CANVAS-R) trials reported significant risk reductions in primary combined major adverse cardiovascular events. Furthermore, regarding renal outcomes, the EMPA-REG Renal OUTCOME and CANVAS program clearly showed improvements in renal outcomes, including decreases in albuminuria and progression of nephropathy, doubling of serum creatinine levels, and initiation of renal replacement therapy.
Potential mechanisms of SGLT2 inhibitors related to renoprotection can be divided into two categories: hemodynamic actions and metabolic actions.
糖尿病肾病（DKD）是导致全球健康负担的最常见的死亡和发病原因。本综述将重点关注钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂的潜在治疗干预措施，这些措施可能预防 DKD 的发生和进展。
SGLT2 抑制剂已被广泛用作抗糖尿病药物。最近的临床研究表明，这些药物在改善血糖控制、高血压和降低体重的同时，降低了 2 型糖尿病患者肾功能损害和心力衰竭的风险。关于长期临床结局，从 CANVAS 和 CANVAS-R（CANVAS-R）试验整合而来的 Empagliflozin、心血管结局和 2 型糖尿病患者的死亡率（EMPA-REG OUTCOME）、EMPA-REG 肾脏结局（EMPA-REG Renal OUTCOME）和卡格列净心血管评估研究（CANVAS）方案报告了主要不良心血管事件的综合风险显著降低。此外，关于肾脏结局，EMPA-REG Renal OUTCOME 和 CANVAS 方案清楚地显示了肾脏结局的改善，包括白蛋白尿减少和肾病进展、血肌酐水平加倍和开始肾脏替代治疗。
SGLT2 抑制剂相关的肾保护潜在机制可分为两类：血流动力学作用和代谢作用。
