Updates for Cardio-Kidney Protective Effects by Angiotensin Receptor-Neprilysin Inhibitor: Requirement for Additional Evidence of Kidney Protection.
Updates for Cardio-Kidney Protective Effects by Angiotensin Receptor-Neprilysin Inhibitor: Requirement for Additional Evidence of Kidney Protection.
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DOI：
10.1161/jaha.122.029565
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发表时间：
2023-04-18
影响因子：
5.4
通讯作者：
Tamura, Kouichi
中科院分区：
文献类型：
--
作者：
Tsukamoto, Shunichiro;Uehara, Tatsuki;Azushima, Kengo;Wakui, Hiromichi;Tamura, Kouichi
关键词：
心力衰竭和慢性肾脏疾病的发病率正在增加，许多患者同时患有这两种疾病。血管紧张素受体-脑啡肽酶抑制剂（ARNI）是治疗这两种疾病的有希望的候选药物。在大型临床试验中，如PARADIGM-HF（ARNI与ACEI [血管紧张素转换酶抑制剂]确定对心力衰竭全球死亡率和发病率的影响的前瞻性比较）试验，ARNI已显示出与肾素-血管紧张素系统抑制剂（RAS-Is）相比具有上级心脏保护作用。也有研究表明，ARNI可以在HF患者中提供超过RAS‐Is的肾保护作用。ARNI可能对肾脏产生有益影响，因为它能够改善心力衰竭患者的心脏功能，并通过增强利尿钠肽等激素的作用来影响肾脏血流动力学。相反，在PARADIGM-HF试验中，ARNI与RAS-I相比与更多的蛋白尿相关;因此，尚不清楚长期ARNI治疗是否具有肾脏保护作用。此外，在英国HARP-III（英国心脏和肾脏保护-III）试验中，ARNI在慢性肾脏疾病患者中没有提供RAS-I以外的肾脏保护作用。换句话说，ARNI比RAS‐I更具肾保护作用的患者人群可能有限。总的来说，ARNI除了心脏保护作用外，还可能具有肾脏保护作用，但迄今为止的证据仅适用于心力衰竭。从理论上讲，考虑到ARNI的分子机制，它在肾硬化等疾病中也可能具有肾脏保护作用，这种疾病的蛋白尿风险较低，肾脏灌注减少，但缺乏这种作用的证据。需要进一步的研究来澄清ARNI治疗是否是一种可接受的肾脏保护治疗策略。
The incidence of heart failure and chronic kidney disease is increasing, and many patients develop both diseases. Angiotensin receptor‐neprilysin inhibitor (ARNI) is a promising therapeutic candidate for both diseases. ARNI has demonstrated superior cardioprotective effects compared with renin–angiotensin system inhibitors (RAS‐Is) in large clinical trials such as the PARADIGM‐HF (Prospective Comparison of ARNI With ACEI [Angiotensin‐Converting Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. It has also been suggested that ARNI can provide renoprotective effects beyond those of RAS‐Is in patients with HF. ARNI might have beneficial effects on the kidneys because of its ability to improve cardiac function in patients with heart failure and affect renal hemodynamics by enhancing the effects of hormones such as natriuretic peptide. In contrast, in the PARADIGM‐HF trial, ARNI was associated with more albuminuria compared with RAS‐I; thus, it is unclear whether long‐term ARNI therapy has renoprotective effects. Additionally, ARNI did not provide renoprotective effects beyond RAS‐I in patients with chronic kidney disease in the UK HARP‐III (United Kingdom Heart and Renal Protection‐III) trial. In other words, the patient population in which ARNI is more renoprotective than RAS‐I might be limited. Collectively, ARNI may have renoprotective effects in addition to cardioprotective effects, but the evidence to date is applicable only to heart failure. Theoretically, given the molecular mechanism of ARNI, it could also be renoprotective in conditions such as nephrosclerosis, which has low risks of albuminuria and reduced kidney perfusion, but the evidence for such effects is lacking. Further research is needed to clarify whether ARNI therapy is an acceptable treatment strategy for renal protection.
DOI：
10.1093/ehjcvp/pvab085
发表时间：
2022-05-05
期刊：
European heart journal. Cardiovascular pharmacotherapy
影响因子：
--
作者：
通讯作者：
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影响因子：
5.6
作者：
Gray EA;Patel SN;Doris PA;Hussain T
通讯作者：
Hussain T