{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:23:31Z","timestamp":1790205811352,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Classical renin\u2013angiotensin 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 \u226550% 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 \u22650.5\u00a0mg\/dL from baseline and a 25% decline in eGFR) and renal impairment (an increase of at least 0.3\u00a0mg\/dL in creatinine levels). Additionally, a subgroup analysis of renal impairment in patients with HFrEF was performed. Secondary outcomes included hyperkalemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results suggested a 31% reduction in renal impairment with ARNI treatment compared with RASI and a 37% reduction in the odds of \u226550% 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ckj\/sfaf224","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T13:27:42Z","timestamp":1752240462000},"source":"Crossref","is-referenced-by-count":9,"title":["Comparative renal effects of angiotensin receptor neprilysin inhibitors and ACEi\/ARB: a systematic review and meta-analysis"],"prefix":"10.1093","volume":"18","author":[{"given":"Adrian","family":"Covic","sequence":"first","affiliation":[{"name":"University of Medicine and Pharmacy \u201cGrigore T. Popa \u201d, Iasi"},{"name":"Hospital \u201cDr C.I. Parhon\u201d \u2013 Department of Nephrology and Renal Transplant, Iasi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luminita","family":"Voroneanu","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy \u201cGrigore T. Popa \u201d, Iasi"},{"name":"Hospital \u201cDr C.I. Parhon\u201d \u2013 Department of Nephrology and Renal Transplant, Iasi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca-Elena","family":"Stefan","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy \u201cGrigore T. Popa \u201d, Iasi"},{"name":"Hospital \u201cDr C.I. Parhon\u201d \u2013 Department of Nephrology and Renal Transplant, Iasi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crischentian","family":"Brinza","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy \u201cGrigore T. Popa \u201d, Iasi"},{"name":"Institute of Cardiovascular Diseases \u201cProf. Dr George I.M. Georgescu\u201d \u2013 Department of Cardiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Covic","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy \u201cGrigore T. Popa \u201d, Iasi"},{"name":"Institute of Cardiovascular Diseases \u201cProf. Dr George I.M. Georgescu\u201d \u2013 Department of Cardiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1297-0675","authenticated-orcid":false,"given":"Mehmet","family":"Kanbay","sequence":"additional","affiliation":[{"name":"Koc University School of Medicine Department of Nephrology, , Istanbul ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viorel","family":"Scripcariu","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy \u201cGrigore T. Popa \u201d, Iasi"},{"name":"Regional Institute of Oncology \u2013 Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Iliescu","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy \u201cGrigore T. Popa \u201d, Iasi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-1588","authenticated-orcid":false,"given":"Alexandru","family":"Burlacu","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy \u201cGrigore T. Popa \u201d, Iasi"},{"name":"Institute of Cardiovascular Diseases \u201cProf. Dr George I.M. Georgescu\u201d \u2013 Department of Cardiology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"2025080109070391300_bib1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of chronic kidney disease: an update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int Suppl"},{"key":"2025080109070391300_bib2","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/ki.2012.208","article-title":"Acute kidney injury and chronic kidney disease: an integrated clinical syndrome","volume":"82","author":"Chawla","year":"2012","journal-title":"Kidney Int"},{"key":"2025080109070391300_bib3","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.15420\/ecr.2021.54","article-title":"Cardiovascular complications of chronic kidney disease: an introduction","volume":"17","author":"Warrens","year":"2022","journal-title":"Eur Cardiol"},{"key":"2025080109070391300_bib4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.5334\/gh.1288","article-title":"The heart of the world","volume":"19","author":"Di Cesare","year":"2024","journal-title":"Glob Heart"},{"key":"2025080109070391300_bib5","doi-asserted-by":"crossref","first-page":"1034170","DOI":"10.3389\/fphys.2023.1034170","article-title":"Role of the renin\u2013angiotensin system in the pathophysiology of coronary heart disease and heart failure: diagnostic biomarkers and therapy with drugs and natural products","volume":"14","author":"Mehta","year":"2023","journal-title":"Front Physiol"},{"key":"2025080109070391300_bib6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/478597","article-title":"Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in patients at high risk of cardiovascular events: a meta-analysis of 10 randomised placebo-controlled trials","volume":"2013","author":"Ong","year":"2013","journal-title":"ISRN Cardiol"},{"key":"2025080109070391300_bib7","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1053\/j.ajkd.2015.10.011","article-title":"Renin-angiotensin system inhibitors and kidney and cardiovascular outcomes in patients with CKD: a Bayesian network meta-analysis of randomized clinical trials","volume":"67","author":"Xie","year":"2016","journal-title":"Am J Kidney Dis"},{"key":"2025080109070391300_bib8","doi-asserted-by":"publisher","first-page":"412","DOI":"10.3390\/jcm10030412","article-title":"Impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on acute kidney injury in emergency medical admissions","volume":"10","author":"Feidakis","year":"2021","journal-title":"J Clin Med"},{"key":"2025080109070391300_bib9","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2025080109070391300_bib10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jacc.2023.04.019","article-title":"Angiotensin-neprilysin inhibition in patients with mildly reduced or preserved ejection fraction and worsening heart failure","volume":"82","author":"Mentz","year":"2023","journal-title":"J Am Coll Cardiol"},{"key":"2025080109070391300_bib11","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1253\/circj.CJ-20-0854","article-title":"Efficacy and safety of sacubitril\/valsartan in Japanese patients with chronic heart failure and reduced ejection fraction\u2014results from the PARALLEL-HF study","volume-title":"Circ J","author":"Tsutsui","year":"2021"},{"key":"2025080109070391300_bib12","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1093\/eurheartj\/ehv186","article-title":"Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients","volume":"36","author":"Desai","year":"2015","journal-title":"Eur Heart J"},{"key":"2025080109070391300_bib13","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1056\/NEJMoa1908655","article-title":"Angiotensin\u2013neprilysin inhibition in heart failure with preserved ejection fraction","volume":"381","author":"Solomon","year":"2019","journal-title":"N Engl J Med"},{"key":"2025080109070391300_bib14","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.jchf.2018.02.004","article-title":"Renal effects and associated outcomes during angiotensin-neprilysin inhibition in heart failure","volume":"6","author":"Damman","year":"2018","journal-title":"JACC Heart Fail"},{"key":"2025080109070391300_bib15","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1016\/S0140-6736(12)61227-6","article-title":"The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial","volume":"380","author":"Solomon","year":"2012","journal-title":"Lancet"},{"key":"2025080109070391300_bib16","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1056\/NEJMoa1812851","article-title":"Angiotensin\u2013neprilysin inhibition in acute decompensated heart failure","volume":"380","author":"Velazquez","year":"2019","journal-title":"N Engl J Med"},{"key":"2025080109070391300_bib17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1001\/jamacardio.2021.4567","article-title":"Effect of treatment with Sacubitril\/valsartan in patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial","volume":"7","author":"Mann","year":"2022","journal-title":"JAMA Cardiol"},{"key":"2025080109070391300_bib18","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1038\/s41440-021-00819-7","article-title":"Efficacy of sacubitril\/valsartan versus olmesartan in Japanese patients with essential hypertension: a randomized, double-blind, multicenter study","volume":"45","author":"Rakugi","year":"2022","journal-title":"Hypertens Res"},{"key":"2025080109070391300_bib19","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1161\/CIRCULATIONAHA.118.034818","article-title":"Effects of sacubitril\/valsartan versus irbesartan in patients with chronic kidney disease: a randomized double-blind trial","volume":"138","author":"Haynes","year":"2018","journal-title":"Circulation"},{"key":"2025080109070391300_bib20","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1161\/CIRCULATIONAHA.118.037077","article-title":"Angiotensin receptor neprilysin inhibitor for functional mitral regurgitation: PRIME study","volume":"139","author":"Kang","year":"2019","journal-title":"Circulation"},{"key":"2025080109070391300_bib21","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1001\/jama.2021.18463","article-title":"Effect of sacubitril\/valsartan vs standard medical therapies on plasma NT-proBNP concentration and submaximal exercise capacity in patients with heart failure and preserved ejection fraction: the PARALLAX randomized clinical Trial","volume":"326","author":"Pieske","year":"2021","journal-title":"JAMA"},{"key":"2025080109070391300_bib22","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1161\/01.CIR.0000029801.86489.50","article-title":"Comparison of omapatrilat and enalapril in patients with chronic heart failure: the omapatrilat versus enalapril randomized trial of utility in reducing events (OVERTURE)","volume":"106","author":"Packer","year":"2002","journal-title":"Circulation"},{"key":"2025080109070391300_bib23","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/S0140-6736(00)02602-7","article-title":"Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial","volume":"356","author":"Rouleau","year":"2000","journal-title":"Lancet"},{"key":"2025080109070391300_bib24","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1111\/jcpt.13243","article-title":"Renal safety and efficacy of angiotensin receptor-neprilysin inhibitor: a meta-analysis of randomized controlled trials","volume":"45","author":"Feng","year":"2020","journal-title":"J Clin Pharm Ther"},{"key":"2025080109070391300_bib25","doi-asserted-by":"publisher","first-page":"447","DOI":"10.4314\/tjpr.v23i2.27","article-title":"Comparative renoprotection: sacubitril\/valsartan versus ACEI or ARB: a systematic review and meta-analysis","volume":"23","author":"Yang","year":"2024","journal-title":"Trop J Pharm Res"},{"key":"2025080109070391300_bib26","doi-asserted-by":"publisher","first-page":"e2432862","DOI":"10.1001\/jamanetworkopen.2024.32862","article-title":"Kidney outcomes following angiotensin receptor-neprilysin inhibitor vs angiotensin-converting enzyme inhibitor\/angiotensin receptor blocker therapy for thrombotic microangiopathy","volume":"7","author":"Li","year":"2024","journal-title":"JAMA Netw Open"},{"key":"2025080109070391300_bib27","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1002\/ejhf.3454","article-title":"Efficacy and safety of angiotensin receptor\u2013neprilysin inhibition in heart failure patients with end-stage kidney disease on maintenance dialysis: a systematic review and meta-analysis","volume":"27","author":"Nguyen","year":"2025","journal-title":"Eur J Heart Fail"},{"key":"2025080109070391300_bib28","doi-asserted-by":"publisher","first-page":"238","DOI":"10.31083\/j.rcm2307238","article-title":"Sacubitril\/valsartan in heart failure and beyond\u2014from molecular mechanisms to clinical relevance","volume":"23","author":"Nikolic","year":"2022","journal-title":"Rev Cardiovasc Med"},{"key":"2025080109070391300_bib29","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1093\/ajh\/hpaf028","article-title":"Switching from ARBs to Sacubitril\/Valsartan safely improves 24-hour ambulatory blood pressure in patients with advanced chronic kidney disease","volume":"38","author":"Kinguchi","year":"2025","journal-title":"Am J Hypertens"}],"container-title":["Clinical Kidney Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ckj\/advance-article-pdf\/doi\/10.1093\/ckj\/sfaf224\/63727904\/sfaf224.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/18\/8\/sfaf224\/63727904\/sfaf224.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/18\/8\/sfaf224\/63727904\/sfaf224.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T13:07:09Z","timestamp":1754053629000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ckj\/article\/doi\/10.1093\/ckj\/sfaf224\/8196616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,11]]},"references-count":29,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ckj\/sfaf224","relation":{},"ISSN":["2048-8505","2048-8513"],"issn-type":[{"value":"2048-8505","type":"print"},{"value":"2048-8513","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,8]]},"published":{"date-parts":[[2025,7,11]]},"article-number":"sfaf224"}}