IIS-Fundacion Jimenez Diaz UAM and School of Medicine, GEENDIAB, UAM, Madrid, Spain.
Institute of Cardiovascular Sciences, University of Birmingham, Birmingham,UK.
Nephrol Dial Transplant. 2023 Jan 23;38(1):10-25. doi: 10.1093/ndt/gfab167.
Diabetic kidney disease (DKD) develops in ∼40% of patients with diabetes and is the most common cause of chronic kidney disease (CKD) worldwide. Patients with CKD, especially those with diabetes mellitus, are at high risk of both developing kidney failure and cardiovascular (CV) death. The use of renin-angiotensin system (RAS) blockers to reduce the incidence of kidney failure in patients with DKD dates back to studies that are now ≥20 years old. During the last few years, sodium-glucose co-transporter-2 inhibitors (SGLT2is) have shown beneficial renal effects in randomized trials. However, even in response to combined treatment with RAS blockers and SGLT2is, the renal residual risk remains high with kidney failure only deferred, but not avoided. The risk of CV death also remains high even with optimal current treatment. Steroidal mineralocorticoid receptor antagonists (MRAs) reduce albuminuria and surrogate markers of CV disease in patients already on optimal therapy. However, their use has been curtailed by the significant risk of hyperkalaemia. In the FInerenone in reducing kiDnEy faiLure and dIsease prOgression in DKD (FIDELIO-DKD) study comparing the actions of the non-steroidal MRA finerenone with placebo, finerenone reduced the progression of DKD and the incidence of CV events, with a relatively safe adverse event profile. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of MRAs, analyses the potential mechanisms involved and discusses their potential future place in the treatment of patients with diabetic CKD.
糖尿病肾病（DKD）在约 40%的糖尿病患者中发展，是全球范围内慢性肾脏病（CKD）最常见的病因。CKD 患者，尤其是合并糖尿病的患者，发生肾衰竭和心血管（CV）死亡的风险均较高。使用肾素-血管紧张素系统（RAS）阻滞剂来降低 DKD 患者的肾衰竭发生率可追溯到现在已有≥20 年历史的研究。在过去几年中，钠-葡萄糖协同转运蛋白 2 抑制剂（SGLT2is）在随机试验中显示出了有益的肾脏作用。然而，即使在联合使用 RAS 阻滞剂和 SGLT2is 进行治疗后，肾衰竭的肾脏残余风险仍然很高，只是将其推迟发生，而非避免发生。即使采用目前最佳的治疗方法，CV 死亡风险仍然很高。甾体类盐皮质激素受体拮抗剂（MRAs）可降低已接受最佳治疗患者的蛋白尿和心血管疾病的替代标志物。然而，由于高钾血症的风险显著增加，其应用受到限制。在比较非甾体 MRA 非奈利酮与安慰剂作用的 FInerenone 在减少 DKD 患者的肾脏失败和疾病进展（FIDELIO-DKD）研究中，非奈利酮降低了 DKD 的进展和 CV 事件的发生率，具有相对安全的不良事件谱。本文详细介绍了 MRA 的心脏保护和肾脏保护作用的现有证据，分析了其中涉及的潜在机制，并讨论了它们在治疗糖尿病性 CKD 患者中的潜在未来地位。
