{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:58:38Z","timestamp":1792799918506,"version":"4.5.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Center for Advancing Translational Sciences of the National Institutes of Health","award":["KL2TR001426"],"award-info":[{"award-number":["KL2TR001426"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Crit Care"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Sepsis-induced endothelial dysfunction is proposed to cause angiotensin-converting enzyme (ACE) dysfunction and renin\u2013angiotensin\u2013aldosterone system (RAAS) derangement, exacerbating vasodilatory shock and acute kidney injury (AKI). Few studies test this hypothesis directly, including none in children. We measured serum ACE concentrations and activity, and assessed their association with adverse kidney outcomes in pediatric septic shock.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A pilot study of 72 subjects aged 1\u00a0week\u201318\u00a0years from an existing multicenter, observational study. Serum ACE concentrations and activity were measured on Day 1; renin\u2009+\u2009prorenin concentrations were available from a previous study. The associations between individual RAAS components and a composite outcome (Day 1\u20137 severe persistent AKI, kidney replacement therapy use, or mortality) were assessed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>50\/72 subjects (69%) had undetectable ACE activity (&lt;\u20092.41 U\/L) on Day 1 and 27\/72 (38%) developed the composite outcome. Subjects with undetectable ACE activity had higher Day 1 renin\u2009+\u2009prorenin compared to those with activity (4533 vs. 2227\u00a0pg\/ml, <jats:italic>p<\/jats:italic>\u2009=\u20090.017); ACE concentrations were no different between groups. Children with the composite outcome more commonly had undetectable ACE activity (85% vs. 65%, <jats:italic>p<\/jats:italic>\u2009=\u20090.025), and had higher Day 1 renin\u2009+\u2009prorenin (16,774\u00a0pg\/ml vs. 3037\u00a0pg\/ml, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and ACE concentrations (149 vs. 96\u00a0pg\/ml, <jats:italic>p<\/jats:italic>\u2009=\u20090.019). On multivariable regression, increasing ACE concentrations (aOR 1.01, 95%CI 1.002\u20131.03, <jats:italic>p<\/jats:italic>\u2009=\u20090.015) and undetectable ACE activity (aOR 6.6, 95%CI 1.2\u201336.1, <jats:italic>p<\/jats:italic>\u2009=\u20090.031) retained associations with the composite outcome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>ACE activity is diminished in pediatric septic shock, appears uncoupled from ACE concentrations, and is associated with adverse kidney outcomes. Further study is needed to validate these findings in larger cohorts.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13054-023-04518-2","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T06:02:01Z","timestamp":1686549721000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Increasing angiotensin-converting enzyme concentrations and absent angiotensin-converting enzyme activity are associated with adverse kidney outcomes in pediatric septic shock"],"prefix":"10.1186","volume":"27","author":[{"given":"Naomi","family":"Pode-Shakked","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Ceschia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Rose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart L.","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalja L.","family":"Stanski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Genomics of Pediatric Septic Shock Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"4518_CR1","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1164\/rccm.201412-2323OC","volume":"191","author":"SL Weiss","year":"2015","unstructured":"Weiss SL, Fitzgerald JC, Pappachan J, Wheeler D, Jaramillo-Bustamante JC, Salloo A, et al. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015;191:1147\u201357.","journal-title":"Am J Respir Crit Care Med"},{"key":"4518_CR2","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1097\/PCC.0000000000000225","volume":"15","author":"F Balamuth","year":"2014","unstructured":"Balamuth F, Weiss SL, Neuman MI, Scott H, Brady PW, Paul R, et al. Pediatric severe sepsis in US children\u2019s hospitals. Pediatr Crit Care Med. 2014;15:798\u2013805.","journal-title":"Pediatr Crit Care Med"},{"key":"4518_CR3","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1097\/CCM.0000000000002007","volume":"44","author":"JC Fitzgerald","year":"2016","unstructured":"Fitzgerald JC, Basu RK, Akcan-Arikan A, Izquierdo LM, Pi\u00f1eres Olave BE, Hassinger AB, et al. Acute kidney injury in pediatric severe sepsis: an independent risk factor for death and new disability. 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Procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation and with the 1964 Declaration of Helsinki and its later amendments. Importantly, this protocol includes approval for future secondary analyses of de-identified data.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"230"}}