治疗糖尿病肾病:现状与未来。

Treatment of Diabetic Kidney Disease: Current and Future.

机构信息

Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

出版信息

Diabetes Metab J. 2021 Jan;45(1):11-26. doi: 10.4093/dmj.2020.0217. Epub 2021 Jan 22.

Abstract

Diabetic kidney disease (DKD) is the major cause of end-stage kidney disease. However, only renin-angiotensin system inhibitor with multidisciplinary treatments is effective for DKD. In 2019, sodium-glucose cotransporter 2 (SGLT2) inhibitor showed efficacy against DKD in Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, adding a new treatment option. However, the progression of DKD has not been completely controlled. The patients with transient exposure to hyperglycemia develop diabetic complications, including DKD, even after normalization of their blood glucose. Temporary hyperglycemia causes advanced glycation end product (AGE) accumulations and epigenetic changes as metabolic memory. The drugs that improve metabolic memory are awaited, and AGE inhibitors and histone modification inhibitors are the focus of clinical and basic research. In addition, incretin-related drugs showed a renoprotective ability in many clinical trials, and these trials with renal outcome as their primary endpoint are currently ongoing. Hypoxia-inducible factor prolyl hydroxylase inhibitors recently approved for renal anemia may be renoprotective since they improve tubulointerstitial hypoxia. Furthermore, NF-E2-related factor 2 activators improved the glomerular filtration rate of DKD patients in Bardoxolone Methyl Treatment: Renal Function in chronic kidney disease/Type 2 Diabetes (BEAM) trial and Phase II Study of Bardoxolone Methyl in Patients with Chronic Kidney Disease and Type 2 Diabetes (TSUBAKI) trial. Thus, following SGLT2 inhibitor, numerous novel drugs could be utilized in treating DKD. Future studies are expected to provide new insights.

摘要

糖尿病肾病(DKD)是终末期肾病的主要原因。然而,只有肾素-血管紧张素系统抑制剂联合多学科治疗对 DKD 有效。2019 年,钠-葡萄糖共转运蛋白 2(SGLT2)抑制剂在卡格列净和糖尿病肾脏疾病中的肾脏事件与已经存在的肾病临床评估(CREDENCE)试验中显示出对 DKD 的疗效,为治疗提供了新的选择。然而,DKD 的进展尚未得到完全控制。即使血糖恢复正常,短暂暴露于高血糖的患者也会发展为糖尿病并发症,包括 DKD。短暂性高血糖会导致晚期糖基化终产物(AGE)积聚和表观遗传改变,即代谢记忆。人们期待改善代谢记忆的药物,AGE 抑制剂和组蛋白修饰抑制剂是临床和基础研究的重点。此外,在许多临床试验中,肠降血糖素相关药物显示出肾脏保护作用,目前正在进行以肾脏结局为主要终点的这些试验。最近批准用于治疗肾性贫血的缺氧诱导因子脯氨酰羟化酶抑制剂可能具有肾脏保护作用,因为它们可以改善肾小管间质缺氧。此外,NF-E2 相关因子 2 激活剂在 Bardoxolone Methyl 治疗:慢性肾脏病/2 型糖尿病患者的肾小球滤过率(BEAM)试验和 Bardoxolone Methyl 在慢性肾脏病和 2 型糖尿病患者中的 II 期研究(TSUBAKI)试验中改善了 DKD 患者的肾小球滤过率。因此,继 SGLT2 抑制剂之后,许多新的药物可用于治疗 DKD。预计未来的研究将提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5144/7850867/a674755b099b/dmj-2020-0217f1.jpg

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