Sacubitril/valsartan in chronic kidney disease: From pharmacological mechanism to clinical application

• Published in: European journal of pharmacology Vol. 907; p. 174288
• Main Authors: Kuang, Huang, Huang, Xin, Zhou, Zhifeng, Cheng, Xuexin, Xu, Gaosi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.09.2021
• Subjects: Adverse events; Aminobutyrates; Biphenyl Compounds; Chronic kidney disease; Clinical application; Drug Combinations; Heart failure; LCZ696; Pharmacological mechanism; Sacubitril/valsartan; Stroke Volume - drug effects; Tetrazoles - pharmacology; Valsartan; Heart failure; Adverse events; Pharmacological mechanism; Clinical application; Sacubitril/valsartan; LCZ696; Chronic kidney disease
• ISSN: 0014-2999; 1879-0712; 1879-0712
• DOI: 10.1016/j.ejphar.2021.174288

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. •Patients with CKD are at a significantly increased risk of cardiovascular disease, which increases the progression of CKD.•Compared with RAS inhibitors, LCZ696 is generally well tolerated and no serious AE is observed.•Future studies should evaluate the impact of LCZ696 on the cognitive function.•More studies should be carried out in patients with CKD alone, to determine the potential efficacy and safety of LCZ696.•LCZ696 can regulate inflammation, oxidative stress and renal fibrosis, and thus play a role in kidney protection.