Providence Health Care, Spokane, WA; University of Washington School of Medicine, Seattle, WA.
Providence Health Care, Spokane, WA.
Am J Kidney Dis. 2018 Aug;72(2):267-277. doi: 10.1053/j.ajkd.2018.03.022. Epub 2018 Jun 14.
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease in the United States and the world alike, and there is a great unmet need for treatments to reduce DKD development and progression. Inhibition of sodium/glucose co-transporter 2 (SGLT2) in the proximal tubule of the kidney has emerged as an effective antihyperglycemic treatment, leading to regulatory approval of several first-generation SGLT2 inhibitors for the treatment of type 2 diabetes. In follow-on clinical trials for the cardiovascular safety of the SGLT2 inhibitors, secondary effects to prevent or reduce albuminuria and decline in estimated glomerular filtration rate spurred further investigation into their potential application in DKD. This review summarizes the current understanding of mechanisms by which SGLT2 inhibitors block glucose reabsorption in the proximal tubule and improve systemic glucose homeostasis, the hypothesized mechanisms for kidney-protective effects of SGLT2 inhibition, and current recommendations for use of this class of antihyperglycemic agents in diabetic patients with low estimated glomerular filtration rates. Results of ongoing clinical trials in patients with DKD are eagerly awaited to expand knowledge of how SGLT2 inhibitors might be used for prevention and treatment.
糖尿病肾病（DKD）是美国乃至全球导致终末期肾病的主要原因，因此非常需要治疗方法来减少 DKD 的发生和进展。抑制肾脏近端小管中的钠/葡萄糖协同转运蛋白 2（SGLT2）已成为一种有效的降糖治疗方法，这导致了几种第一代 SGLT2 抑制剂获得批准，可用于治疗 2 型糖尿病。在 SGLT2 抑制剂的心血管安全性的后续临床试验中，预防或减少白蛋白尿和估计肾小球滤过率下降的次要作用促使人们进一步研究其在 DKD 中的潜在应用。这篇综述总结了 SGLT2 抑制剂阻断近端小管中葡萄糖重吸收并改善全身葡萄糖稳态的机制、SGLT2 抑制的肾脏保护作用的假设机制，以及目前在肾小球滤过率较低的糖尿病患者中使用这类降糖药物的建议。目前正在等待 DKD 患者的临床试验结果，以扩大对 SGLT2 抑制剂在预防和治疗中的应用的认识。
