Covic Adrian, Voroneanu Luminita, Stefan Anca-Elena, Brinza Crischentian, Covic Alexandra, Kanbay Mehmet, Scripcariu Viorel, Iliescu Stefan, Burlacu Alexandru
University of Medicine and Pharmacy "Grigore T. Popa", Iasi.
Hospital "Dr C.I. Parhon" - Department of Nephrology and Renal Transplant, Iasi.
Clin Kidney J. 2025 Jul 11;18(8):sfaf224. doi: 10.1093/ckj/sfaf224. eCollection 2025 Aug.
Classical renin-angiotensin system inhibitors (RASI), such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), have long been the foundation of treatment for patients with cardiovascular disease (CVD) and chronic kidney disease (CKD). The development of angiotensin receptor neprilysin inhibitors (ARNI) has introduced a valuable therapeutic option for patients with heart failure with reduced ejection fraction (HFrEF), reducing the risk of major cardiovascular events and becoming an essential component of treatment for this population. However, their effects on renal outcomes remain uncertain.
We conducted a systematic review and meta-analysis to compare the renal effects of ARNI and RASI. Relevant studies were searched in the following databases from inception to 30 December 2024: MEDLINE (PubMed), Embase and Scopus. The primary outcomes assessed were: a ≥50% reduction in estimated glomerular filtration rate (eGFR) or progression to end-stage renal disease (ESRD), a composite measure of worsening renal function (serum creatinine increase of ≥0.5 mg/dL from baseline and a 25% decline in eGFR) and renal impairment (an increase of at least 0.3 mg/dL in creatinine levels). Additionally, a subgroup analysis of renal impairment in patients with HFrEF was performed. Secondary outcomes included hyperkalemia.
Our results suggested a 31% reduction in renal impairment with ARNI treatment compared with RASI and a 37% reduction in the odds of ≥50% decline in eGFR or ESRD. However, the pooled analysis for worsening renal function and hyperkalemia showed no apparent difference between ARNI and RASI. A subgroup analysis on a population with a reduced ejection fraction suggested a 37% lower odds of renal impairment with ARNI when compared with RASI. This study represents the largest and first systematic review and meta-analysis with clearly defined renal outcomes.
Given that ARNI has been explored for indications beyond heart failure, further randomized controlled trials are needed to understand its renal effects better. Future research should determine whether ARNI provides a benefit in a purely CKD population or in a cardio-renal population, given that CVD is the leading cause of mortality in CKD patients.
经典的肾素 - 血管紧张素系统抑制剂（RASI），如血管紧张素转换酶抑制剂（ACEi）和血管紧张素受体阻滞剂（ARB），长期以来一直是心血管疾病（CVD）和慢性肾脏病（CKD）患者治疗的基础。血管紧张素受体脑啡肽酶抑制剂（ARNI）的出现为射血分数降低的心力衰竭（HFrEF）患者引入了一种有价值的治疗选择，降低了重大心血管事件的风险，并成为该人群治疗的重要组成部分。然而，它们对肾脏结局的影响仍不确定。
我们进行了一项系统评价和荟萃分析，以比较ARNI和RASI对肾脏的影响。从数据库创建到2024年12月30日，在以下数据库中检索相关研究：MEDLINE（PubMed）、Embase和Scopus。评估的主要结局包括：估计肾小球滤过率（eGFR）降低≥50%或进展为终末期肾病（ESRD）、肾功能恶化的综合指标（血清肌酐较基线增加≥0.5mg/dL且eGFR下降25%）和肾功能损害（肌酐水平至少增加0.3mg/dL）。此外，对HFrEF患者的肾功能损害进行了亚组分析。次要结局包括高钾血症。
我们的结果表明，与RASI相比，ARNI治疗使肾功能损害降低31%，eGFR降低≥50%或ESRD的几率降低37%。然而，关于肾功能恶化和高钾血症的汇总分析显示，ARNI和RASI之间没有明显差异。对射血分数降低人群的亚组分析表明，与RASI相比，ARNI导致肾功能损害的几率低37%。本研究是最大且首个对明确的肾脏结局进行的系统评价和荟萃分析。
鉴于已对ARNI用于心力衰竭以外的适应症进行了探索，需要进一步开展随机对照试验以更好地了解其对肾脏的影响。鉴于心血管疾病是CKD患者死亡的主要原因未来的研究应确定ARNI在单纯的CKD人群或心肾人群中是否有益。
