Section of Nephrology, University of Illinois at Chicago College of Medicine, Chicago, IL, USA.
US Medical Affairs, Cardiovascular and Renal, Bayer US LLC, Pharmaceuticals, Whippany, NJ, USA.
Expert Rev Clin Pharmacol. 2022 May;15(5):501-513. doi: 10.1080/17512433.2022.2094770. Epub 2022 Jul 3.
Approximately 40% of people with type 2 diabetes (T2D) also have chronic kidney disease (CKD), which substantially increases their risk of cardiovascular (CV)-related complications and mortality. Until recently, no approved therapies have directly targeted inflammatory and fibrotic pathways that drive disease progression and organ damage in patients with CKD associated with T2D.
Finerenone is a potent, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA) that targets fibrosis and inflammation by blocking overactivation of the MR in the kidneys and heart. Finerenone has been associated with significant reductions in kidney- and CV-related endpoints compared with placebo and minimal effects on serum potassium and kidney function in phase III trials involving >13,000 patients with diabetic kidney disease (DKD). In addition to reviewing the clinical data, this review compares the properties of finerenone with those of the older steroidal MRAs spironolactone and eplerenone.
Unlike spironolactone and eplerenone, finerenone has demonstrated a favorable benefit-risk profile offering an effective new treatment for patients with CKD associated with T2D. Increases in serum potassium are predictable and manageable and should not discourage the use of finerenone in clinical practice. It is important to discuss where finerenone 'fits best' within the current DKD management landscape.
约 40%的 2 型糖尿病(T2D)患者同时患有慢性肾脏病(CKD),这大大增加了他们发生心血管(CV)相关并发症和死亡的风险。直到最近,还没有批准的疗法能够直接针对炎症和纤维化途径,这些途径会推动与 T2D 相关的 CKD 患者的疾病进展和器官损伤。
非奈利酮是一种有效的、选择性的、非甾体类盐皮质激素受体拮抗剂(MRA),通过阻断肾脏和心脏中 MR 的过度激活,靶向纤维化和炎症。与安慰剂相比,非奈利酮与肾脏和 CV 相关终点的显著降低相关,并且在涉及 >13000 例糖尿病肾病(DKD)患者的 III 期试验中对血清钾和肾功能的影响最小。除了审查临床数据外,本综述还比较了非奈利酮与较老的甾体类 MRA 螺内酯和依普利酮的特性。
与螺内酯和依普利酮不同,非奈利酮表现出有利的风险效益比,为 T2D 相关 CKD 患者提供了一种有效的新治疗方法。血清钾升高是可预测和可管理的,不应阻止在临床实践中使用非奈利酮。重要的是要讨论非奈利酮在当前 DKD 管理领域中“最适合”的位置。