Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, 100034, China.
Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Eur J Pharmacol. 2021 Sep 15;907:174288. doi: 10.1016/j.ejphar.2021.174288. Epub 2021 Jun 30.
Chronic kidney disease (CKD) is an irreversible, progressive disease characterized by persistent kidney damage, and significantly increased risks of cardiovascular event. However, therapeutic strategies to prevent or slow the progression of CKD remain limited. Sacubitril/valsartan (LCZ696), the representative of the first novel angiotensin receptor-neprilysin inhibitor, has been incorporated into clinical practice guidelines for improving outcomes as a milestone in patients with heart failure. Considering the complex and close relationship between CKD and heart failure, LCZ696 may be beneficial in the treatment of CKD. This review summarizes the pharmacological mechanism and clinical application of LCZ696 in patients with CKD, including its effect on cardiovascular risk and renal outcome, together with potential adverse events. Additionally, due to the influence of serum creatinine and estimated glomerular filtration rate on LCZ696 in patients with heart failure, we also discussed the effects of LCZ696 in patients with advanced CKD and end-stage renal disease. It should be noted that, current clinical studies on LCZ696 are mostly carried out in patients with heart failure, and renal indicators are selected as secondary outcomes. Therefore, more researches should be conducted in patients with CKD alone in the future, to determine the efficacy and safety of LCZ696 in patients with CKD.
慢性肾脏病(CKD)是一种不可逆的、进行性疾病,其特征为持续的肾脏损伤,并显著增加心血管事件的风险。然而,预防或减缓 CKD 进展的治疗策略仍然有限。沙库巴曲缬沙坦(LCZ696),作为首个新型血管紧张素受体-脑啡肽酶抑制剂的代表,已被纳入心力衰竭患者改善预后的临床实践指南,成为一个里程碑。考虑到 CKD 和心力衰竭之间复杂而密切的关系,LCZ696 可能对 CKD 的治疗有益。这篇综述总结了 LCZ696 在 CKD 患者中的药理学机制和临床应用,包括其对心血管风险和肾脏结局的影响,以及潜在的不良反应。此外,由于血清肌酐和估计肾小球滤过率对心力衰竭患者中 LCZ696 的影响,我们还讨论了 LCZ696 在晚期 CKD 和终末期肾病患者中的作用。需要注意的是,目前关于 LCZ696 的临床研究大多是在心力衰竭患者中进行的,而肾脏指标则被选为次要结局。因此,未来应该在单独的 CKD 患者中进行更多的研究,以确定 LCZ696 在 CKD 患者中的疗效和安全性。