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慢性肾脏病和 2 型糖尿病患者中盐皮质激素受体拮抗剂的心脏肾脏获益:FIGARO-DKD 试验的启示。

Cardiorenal benefits of mineralocorticoid antagonists in CKD and type 2 diabetes : Lessons from the FIGARO-DKD trial.

机构信息

Hannover Medical School MHH, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Mount Desert Island Biological Laboratory MDIBL, Bar Harbor, USA.

出版信息

Herz. 2022 Oct;47(5):401-409. doi: 10.1007/s00059-022-05138-2. Epub 2022 Sep 12.

Abstract

Diabetic kidney disease (DKD) develops in almost half of all patients with diabetes and is the most common cause of chronic kidney disease (CKD) worldwide. Despite the high risk of chronic renal failure in these patients, only few therapeutic strategies are available. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with DKD was established years ago and remains the hallmark of therapy. The past 2 years have seen a dramatic change in our therapeutic arsenal for CKD. Sodium-glucose co-transporter‑2 inhibitors (SGLT2s) have been successfully introduced for the treatment of CKD. A further addition is a novel compound antagonizing the activation of the mineralocorticoid receptor: finerenone. Finerenone reduces albuminuria and surrogate markers of cardiovascular disease in patients who are already on optimal therapy. In the past, treatment with other mineralocorticoid receptor antagonists was hampered by a significantly increased risk of hyperkalemia. Finerenone had a much smaller effect on hyperkalemia. Together with a reduced effect on blood pressure and no signs of gynecomastia, this therapeutic strategy had a more specific anti-inflammatory effect and a smaller effect on the volume/electrolyte axis. In the FIDELIO-DKD study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of DKD and the incidence of cardiovascular events, with a relatively safe adverse event profile. In this article, we summarize the available evidence on the cardioprotective and nephroprotective effects of finerenone and analyze the molecular mechanisms involved. In addition, we discuss the potential future role of mineralocorticoid receptor inhibition in the treatment of patients with diabetic CKD.

摘要

糖尿病肾病(DKD)几乎发生在所有糖尿病患者的一半中,是全球范围内慢性肾脏病(CKD)的最常见原因。尽管这些患者发生慢性肾衰竭的风险很高,但可用的治疗策略却很少。多年前已确立使用肾素-血管紧张素系统阻滞剂降低 DKD 患者肾衰竭的发生率,这仍然是治疗的标志。在过去的 2 年中,我们的 CKD 治疗武器库发生了巨大变化。钠-葡萄糖共转运蛋白 2 抑制剂(SGLT2s)已成功用于 CKD 的治疗。另一种新化合物是拮抗盐皮质激素受体激活的药物:非奈利酮。非奈利酮可降低已接受最佳治疗的患者的蛋白尿和心血管疾病替代标志物。过去,由于高钾血症的风险显著增加,使用其他盐皮质激素受体拮抗剂治疗受到阻碍。非奈利酮对高钾血症的影响较小。与对血压的影响较小且没有男性乳房发育的迹象一起,这种治疗策略具有更特异的抗炎作用,对体积/电解质轴的影响较小。在 FIDELIO-DKD 研究中,比较了非甾体盐皮质激素受体拮抗剂非奈利酮与安慰剂的作用,非奈利酮降低了 DKD 的进展和心血管事件的发生率,具有相对安全的不良事件谱。本文总结了非奈利酮的心脏保护和肾脏保护作用的现有证据,并分析了涉及的分子机制。此外,我们还讨论了盐皮质激素受体抑制在治疗糖尿病 CKD 患者中的潜在未来作用。

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