Clinical Trials Service Unit.
Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, Richard Doll Building, Old Road Campus, Oxford, UK.
Curr Opin Nephrol Hypertens. 2021 Jan;30(1):123-130. doi: 10.1097/MNH.0000000000000659.
Chronic kidney disease (CKD) is associated with increased risk of progression to end-stage kidney disease and cardiovascular events. There is limited evidence that available treatments have beneficial effects on cardiorenal outcomes in all people with nondiabetic CKD. Neprilysin inhibition (NEPi) is a new therapeutic strategy with potential to improve outcomes for patients with CKD.
NEPi enhances the activity of the natriuretic peptide system producing natriuresis, diuresis and inhibition of the renin-angiotensin system and sympathetic nervous system. Sacubitril/valsartan is the first Angiotensin receptor-neprilysin inhibitor (ARNI) to be produced and has been shown to substantially improve cardiovascular outcomes in heart failure and delay progression of kidney disease in this population. Although ARNIs have not shown similar effects on kidney function in the short-to-medium term in people with CKD, they are associated with substantial reductions in cardiac biomarkers and blood pressure in CKD.
These data suggest that NEPi with an ARNI could benefit patients with CKD by reducing the risk of cardiovascular disease and have the possibility of retarding the progression of CKD (hence delaying the need for renal replacement therapy).
慢性肾脏病(CKD)与进展为终末期肾病和心血管事件的风险增加有关。有有限的证据表明,现有的治疗方法对所有非糖尿病 CKD 患者的心血肾结局有有益的影响。肾素抑制剂(NEPi)是一种新的治疗策略,有可能改善 CKD 患者的结局。
NEPi 增强了利钠肽系统的活性,产生利钠、利尿和抑制肾素-血管紧张素系统和交感神经系统。沙库巴曲缬沙坦是第一个被生产的血管紧张素受体肾素抑制剂(ARNI),并已被证明在心力衰竭患者中显著改善心血管结局,并延缓该人群的肾脏疾病进展。尽管 ARNIs 在 CKD 患者的短至中期内对肾功能没有类似的影响,但它们与 CKD 中心脏生物标志物和血压的显著降低有关。
这些数据表明,NEPi 与 ARNI 联合使用可能通过降低心血管疾病的风险使 CKD 患者受益,并有可能延缓 CKD 的进展(从而延迟肾脏替代治疗的需要)。