{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T12:22:50Z","timestamp":1783167770069,"version":"3.54.6"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The renal effects of sacubitril\/valsartan (Sac\/Val) in heart failure (HF) remain incompletely defined, partly because kidney outcomes in pivotal HF trials have been variably prespecified and heterogeneously defined. We performed an updated systematic review and meta-analysis to assess whether the apparent renal signal of Sac\/Val varies according to endpoint definition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This updated systematic review was conducted in accordance with PRISMA 2020. Building on the pre-existing evidence base from prior meta-analyses, we performed an updated search of PubMed and Web of Science. Randomized controlled trials (RCTs) and observational comparative studies in adults with HF comparing Sac\/Val with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or standard care were included if renal outcome data were extractable. Renal outcomes were analysed using a hierarchical cross-endpoint approach, including sustained \u226550% estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease (ESKD), composite kidney outcomes, and annualized eGFR decline. Random-effects meta-analysis was performed, with Hartung-Knapp and RCT-only sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 13 study-level reports comprising 34 969 patients were included. Sac\/Val was associated with a lower risk of sustained 50% eGFR decline (risk ratio [RR] 0.68, 95% confidence interval [CI] 0.57\u20130.82) and composite kidney outcome (RR 0.70, 95% CI 0.58\u20130.84), with the composite endpoint showing the most robust and consistent signal, including in RCT-only analyses. By contrast, the association for ESKD alone was directionally favourable but not statistically significant (RR 0.80, 95% CI 0.64\u20131.00). Sac\/Val was also associated with a slower annualized eGFR decline (MD 0.52\u2005mL\/min\/1.73\u2005m2\/year, 95% CI 0.35\u20130.69).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The renal signal associated with Sac\/Val in HF appeared at least partly dependent on endpoint definition. Composite kidney outcomes may best capture its potential nephroprotective effect, with sustained 50% eGFR decline showing a consistent pattern, whereas isolated ESKD remains inconclusive. These findings support a potential nephroprotective role of ARNIs but future research are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eschf\/xvag148","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:45:22Z","timestamp":1780659922000},"source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of ARNIs on hard renal outcomes in heart failure with and without chronic kidney disease: when endpoint definition matters\u2014an updated meta-analysis"],"prefix":"10.1093","volume":"13","author":[{"given":"Giuseppe","family":"Cianciolo","sequence":"first","affiliation":[{"name":"Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-6202","authenticated-orcid":false,"given":"Daniele","family":"Vetrano","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Science (DIMEC), Alma Mater Studiorum\u2014University of Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Tomassetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Science (DIMEC), Alma Mater Studiorum\u2014University of Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Tringali","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, ASL TO4 , Turin ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-5062","authenticated-orcid":false,"given":"Massimo","family":"Iacoviello","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Foggia , Foggia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Marazia","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ospedale V Fazzi, ASL Lecce, Lecce ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Fucili","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Azienda Ospedaliero-Universitaria di Ferrara , Cona, Ferrara ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5473-8551","authenticated-orcid":false,"given":"Gaetano","family":"La Manna","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna ,","place":["Italy"]},{"name":"Department of Medical and Surgical Science (DIMEC), Alma Mater Studiorum\u2014University of Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"De Pascalis","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis, and Renal Transplantation Unit, Vito Fazzi Hospital , 73100 Lecce ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"2026070408114712700_xvag148-B1","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/s41569-024-01046-6","article-title":"Global epidemiology of heart failure","volume":"21","author":"Khan","year":"2024","journal-title":"Nat Rev 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