PDF(Pubmed)
Abstract：
Chronic kidney disease (CKD) is one of the most frequent complications associated with type 2 diabetes mellitus (T2DM) and is also an independent risk factor for cardiovascular disease. The mineralocorticoid receptor (MR) is a nuclear receptor expressed in many tissue types, including kidney and heart. Aberrant and long-term activation of MR by aldosterone in patients with T2DM triggers detrimental effects (eg, inflammation and fibrosis) in these tissues. The suppression of aldosterone at the early stage of T2DM has been a therapeutic strategy for patients with T2DM-associated CKD. Although patients have been treated with renin-angiotensin system (RAS) blockers for decades, RAS blockers alone are not sufficient to prevent CKD progression. Steroidal MR antagonists (MRAs) have been used in combination with RAS blockers; however, undesired adverse effects have restricted their usage, prompting the development of nonsteroidal MRAs with better target specificity and safety profiles. Recently conducted studies, Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) and Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD), have reported that finerenone, a nonsteroidal MRA, improves both renal and cardiovascular outcomes compared with placebo. In this article, we review the history of MRA development and discuss the possibility of its combination with other treatment options, such as sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and potassium binders for patients with T2DM-associated CKD.
摘要：
慢性肾脏病（CKD）是2型糖尿病（T2DM）最常见的并发症之一，也是心血管疾病的独立危险因素。盐皮质激素受体（MR）是在许多组织类型中表达的核受体，包括肾脏和心脏.醛固酮对T2DM患者的MR异常和长期激活会引发不利影响（例如，炎症和纤维化）在这些组织中。在T2DM早期抑制醛固酮已成为T2DM相关CKD患者的治疗策略。尽管患者已经接受肾素-血管紧张素系统（RAS）阻滞剂治疗数十年，单独的RAS阻断剂不足以预防CKD进展。类固醇MR拮抗剂（MRAs）已与RAS阻滞剂联合使用；然而，不希望的不利影响限制了它们的使用，促使开发具有更好目标特异性和安全性的非甾体MRA。最近进行的研究，Finenerone减少糖尿病肾病的肾衰竭和疾病进展（FIDELIO-DKD）和Finenerone减少糖尿病肾病的心血管死亡率和发病率（FIGARO-DKD），已经报告了Finerenone，非甾体MRA,与安慰剂相比,改善肾脏和心血管结局.在这篇文章中,我们回顾了MRA的发展历史，并讨论了其与其他治疗方案相结合的可能性，如钠-葡萄糖协同转运蛋白2抑制剂，胰高血糖素样肽-1受体激动剂,和2型糖尿病相关CKD患者的钾结合剂。
