Salukhov V V, Shamkhalova M S, Duganova A V
Kirov Military Medical Academy.
Endocrinology Research Centre.
Ter Arkh. 2023 Apr 26;95(3):261-273. doi: 10.26442/00403660.2023.03.202152.
Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus and an independent risk factor for cardiovascular disease. Despite guideline-directed therapy of CKD in patients with type 2 diabetes, the risk of renal failure and cardiovascular events still remains high. To date, current medications for CKD haven't reduced enough the residual risk associated with inflammation and fibrosis in patients with type 2 diabetes. Here, in this review we present the results of FIDELIO-DKD, FIGARO-DKD trials and their pooled analysis FIDELITY, aimed to evaluate the effectiveness and safety of selective non-steroidal mineralocorticoid receptor antagonist finerenone in patients with type 2 diabetes with wide range stages of CKD. Modern pathophysiological aspects of mineralocorticoid receptor hyperactivation and features of their blockade by steroidal and nonsteroidal mineralocorticoid receptor antagonists are considered, differences in pharmacological effects between them are also discussed, finerenone benefits and its adverse events, demonstrated in randomized clinical trials are considered here. The probable mechanisms of early and delayed action of finerenone, which were realized in beneficial cardiovascular and renal outcomes in patients with type 2 diabetes with CKD, are presented here. Practical points for finerenone initiation and titration are indicated, aimed to minimize the hyperkalemia risk. Current guidelines for CKD treatment in patients with type 2 diabetes are analyzed, the finerenone placement in combined nephroprotective therapy is determined.
慢性肾脏病(CKD)是糖尿病最常见的并发症之一,也是心血管疾病的独立危险因素。尽管针对2型糖尿病患者的CKD有指南指导的治疗,但肾衰竭和心血管事件的风险仍然很高。迄今为止,目前用于CKD的药物尚未充分降低2型糖尿病患者与炎症和纤维化相关的残余风险。在此综述中,我们展示了FIDELIO-DKD、FIGARO-DKD试验的结果及其汇总分析FIDELITY,旨在评估选择性非甾体类盐皮质激素受体拮抗剂非奈利酮在广泛CKD阶段的2型糖尿病患者中的有效性和安全性。我们考虑了盐皮质激素受体过度激活的现代病理生理学方面以及甾体和非甾体类盐皮质激素受体拮抗剂对其的阻断特征,还讨论了它们之间药理作用的差异,在此考虑了非奈利酮在随机临床试验中显示的益处及其不良事件。本文介绍了非奈利酮在患有CKD的2型糖尿病患者中实现有益心血管和肾脏结局的早期和延迟作用的可能机制。指出了非奈利酮起始和滴定的实用要点,旨在将高钾血症风险降至最低。分析了2型糖尿病患者CKD治疗的当前指南,确定了非奈利酮在联合肾脏保护治疗中的地位。