{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T21:55:35Z","timestamp":1793310935034,"version":"4.5.0"},"reference-count":25,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Sepsis-associated acute kidney injury (SA-AKI) is a common and clinically important condition in patients who are critically ill. Dysregulated inflammation may contribute to it. Intravenous hydrocortisone may decrease the risk of SA-AKI progression.<\/jats:p><\/jats:sec>Objective<\/jats:title>To describe the associations of hydrocortisone use with the incidence and outcomes of requirement for kidney replacement therapy (KRT), as well as source of sepsis, mean arterial pressure (MAP), and MAP indexed to required vasopressor (norepinephrine equivalent [NEE]).<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This cohort study was conducted as a post hoc analysis of the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) randomized clinical trial (RCT), a multicenter placebo-controlled RCT of hydrocortisone in patients with septic shock in 69 intensive care units in Australia, the United Kingdom, New Zealand, Saudi Arabia, and Denmark that recruited between 2013 and 2017. Participants were patients enrolled in the ADRENAL study with septic shock who did not require KRT in the 24 hours prior to randomization and who did not have a prior longstanding dialysis requirement. Data were analyzed between July and September 2024.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Receipt of hydrocortisone (vs placebo), MAP at enrollment, vasopressor dose (NEE) and MAP:NEE ratio, source of sepsis, causative organism, bacteremia, and the use of nephrotoxic antimicrobials, vasopressin, or specific inotropes.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Outcomes of interest were KRT requirement and liberation from KRT, measured as days alive and free of KRT.<\/jats:p><\/jats:sec>Results<\/jats:title>A cohort of 3161 patients (median [IQR] age, 65 [53-74] years, 1921 [61%] male) was identified, including 1589 patients randomized to receive hydrocortisone and 1572 patients who received the placebo. Allocation to treatment with hydrocortisone was associated with a significantly reduced incidence of KRT requirement compared with placebo (329 patients [21%] vs 372 patients [24%]; odds ratio [OR], 0.84 [95% CI, 0.70 to 0.99]; P<\/jats:italic>\u2009=\u2009.04). When controlled for factors associated with KRT requirement, randomization to hydrocortisone remained significantly associated with a reduced odds of new KRT requirement (OR, 0.79 [95% CI, 0.66 to 0.95]; P<\/jats:italic>\u2009=\u2009.01). Among patients who started KRT following randomization, hydrocortisone was not associated with reduced days alive and free of KRT (mean difference, 1.28 [95% CI, \u22124.31 to 6.87] days; P<\/jats:italic>\u2009=\u2009.65).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this post hoc cohort study of patients with septic shock enrolled in a large RCT, intravenous hydrocortisone was associated with a reduced risk of new KRT requirement following randomization.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.12279","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T15:00:23Z","timestamp":1748358023000},"page":"e2512279","source":"Crossref","is-referenced-by-count":15,"title":["Hydrocortisone and Risk Factors for Kidney Replacement Therapy in Septic Shock"],"prefix":"10.1001","volume":"8","author":[{"given":"Lachlan H.","family":"Donaldson","sequence":"first","affiliation":[{"name":"The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia"},{"name":"Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, St Leonards, Australia"},{"name":"Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Devaux","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle C.","family":"White","sequence":"additional","affiliation":[{"name":"Princess Alexandra and Wesley Hospitals, Brisbane, Australia"},{"name":"School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorrilyn","family":"Rajbhandari","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Cohen","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia"},{"name":"The Wesley Hospital, Brisbane, Australia"},{"name":"Faculty of Medicine, University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinaldo","family":"Bellomo","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Austin Hospital, Melbourne, Australia"},{"name":"Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia"},{"name":"Department of Critical Care, The University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Myburgh","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia"},{"name":"Department of Intensive Care Medicine, St George Hospital, Kogarah, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Hammond","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia"},{"name":"Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, St Leonards, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balasubramanian","family":"Venkatesh","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia"},{"name":"Department of Intensive Care Medicine, Gold Coast University Hospital, Southport, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"issue":"9","key":"zoi250413r1","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1007\/s00134-023-07138-0","article-title":"Sepsis-associated acute kidney injury in the intensive care unit: incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes\u2014a multicenter, observational study.","volume":"49","author":"White","year":"2023","journal-title":"Intensive Care Med"},{"issue":"8","key":"zoi250413r2","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1097\/CCM.0000000000006284","article-title":"Quantifying the impact of alternative definitions of sepsis-associated acute kidney injury on its incidence and outcomes: a systematic review and meta-analysis.","volume":"52","author":"Donaldson","year":"2024","journal-title":"Crit Care Med"},{"issue":"1","key":"zoi250413r3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/SHK.0000000000000052","article-title":"A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury.","volume":"41","author":"Gomez","year":"2014","journal-title":"Shock"},{"issue":"11","key":"zoi250413r4","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1038\/sj.ki.5000440","article-title":"Renal blood flow in experimental septic acute renal failure.","volume":"69","author":"Langenberg","year":"2006","journal-title":"Kidney Int"},{"issue":"1","key":"zoi250413r5","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1093\/ndt\/gfad142","article-title":"Sepsis-associated acute kidney injury-treatment standard.","volume":"39","author":"Zarbock","year":"2023","journal-title":"Nephrol Dial Transplant"},{"issue":"6","key":"zoi250413r6","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2300034","article-title":"Patient-level meta-analysis of low-dose hydrocortisone in adults with septic shock.","volume":"2","author":"Pirracchio","year":"2023","journal-title":"NEJM Evid"},{"issue":"9","key":"zoi250413r7","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1056\/NEJMoa1705835","article-title":"Adjunctive glucocorticoid therapy in patients with septic shock.","volume":"378","author":"Venkatesh","year":"2018","journal-title":"N Engl J Med"},{"issue":"9","key":"zoi250413r8","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1056\/NEJMoa1705716","article-title":"Hydrocortisone plus fludrocortisone for adults with septic shock.","volume":"378","author":"Annane","year":"2018","journal-title":"N Engl J Med"},{"issue":"17","key":"zoi250413r9","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1001\/jama.2016.14799","article-title":"Effect of hydrocortisone on development of shock among patients with severe sepsis: the HYPRESS randomized clinical trial.","volume":"316","author":"Keh","year":"2016","journal-title":"JAMA"},{"issue":"5","key":"zoi250413r10","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1001\/jama.2016.10485","article-title":"Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial.","volume":"316","author":"Gordon","year":"2016","journal-title":"JAMA"},{"issue":"12","key":"zoi250413r11","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1016\/j.ajem.2017.06.004","article-title":"Early initiation of low-dose hydrocortisone treatment for septic shock in adults: a randomized clinical trial.","volume":"35","author":"Lv","year":"2017","journal-title":"Am J Emerg Med"},{"issue":"10","key":"zoi250413r12","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1097\/00003246-198510000-00009","article-title":"APACHE II: a severity of disease classification system.","volume":"13","author":"Knaus","year":"1985","journal-title":"Crit Care Med"},{"issue":"1","key":"zoi250413r13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13054-023-04322-y","article-title":"An updated \u201cnorepinephrine equivalent\u201d score in intensive care as a marker of shock severity.","volume":"27","author":"Kotani","year":"2023","journal-title":"Crit Care"},{"issue":"1","key":"zoi250413r14","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/s00134-019-05837-1","article-title":"Characterization and validation of a novel measure of septic shock severity.","volume":"46","author":"Bosch","year":"2020","journal-title":"Intensive Care Med"},{"issue":"9","key":"zoi250413r15","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1007\/s00134-020-06169-1","article-title":"Health-related quality of life in survivors of septic shock: 6-month follow-up from the ADRENAL trial.","volume":"46","author":"Hammond","year":"2020","journal-title":"Intensive Care Med"},{"issue":"3","key":"zoi250413r16","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0168-8510(90)90421-9","article-title":"EuroQol\u2013a new facility for the measurement of health-related quality of life.","volume":"16","author":"EuroQol Group","year":"1990","journal-title":"Health Policy"},{"issue":"6","key":"zoi250413r17","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1002\/hec.2953","article-title":"An Australian discrete choice experiment to value eq-5d health states.","volume":"23","author":"Viney","year":"2014","journal-title":"Health Econ"},{"issue":"6","key":"zoi250413r18","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1097\/CCM.0000000000000212","article-title":"The interaction of vasopressin and corticosteroids in septic shock: a pilot randomized controlled trial.","volume":"42","author":"Gordon","year":"2014","journal-title":"Crit Care Med"},{"issue":"1","key":"zoi250413r19","doi-asserted-by":"publisher","DOI":"10.1097\/CCE.0000000000001000","article-title":"Corticosteroids in sepsis and septic shock: a systematic review, pairwise, and dose-response meta-analysis.","volume":"6","author":"Pitre","year":"2024","journal-title":"Crit Care Explor"},{"issue":"4","key":"zoi250413r20","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.bbrc.2013.05.042","article-title":"Glucocorticoids attenuate septic acute kidney injury.","volume":"435","author":"Choi","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"key":"zoi250413r21","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2022.101915","article-title":"Hydrocortisone alleviates sepsis-induced acute kidney injury through HSF-1-mediated transcriptional suppression of XPO1.","volume":"79","author":"Jin","year":"2022","journal-title":"Tissue Cell"},{"key":"zoi250413r22","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2023.109738","article-title":"The polarization of M2 macrophages can be adjusted to alleviate renal injury by methylprednisolone in sepsis-AKI.","volume":"747","author":"Ma","year":"2023","journal-title":"Arch Biochem Biophys"},{"issue":"6","key":"zoi250413r23","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1007\/s11255-023-03908-3","article-title":"Mean arterial pressure to norepinephrine equivalent dose ratio for predicting renal replacement therapy requirement: a retrospective analysis from the MIMIC-IV.","volume":"56","author":"Liu","year":"2024","journal-title":"Int Urol Nephrol"},{"issue":"6","key":"zoi250413r24","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1097\/CCM.0000000000003092","article-title":"Outcomes in patients with vasodilatory shock and renal replacement therapy treated with intravenous angiotensin II.","volume":"46","author":"Tumlin","year":"2018","journal-title":"Crit Care Med"},{"issue":"1","key":"zoi250413r25","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s13054-024-04877-4","article-title":"Sepsis-associated acute kidney injury: recent advances in enrichment strategies, sub-phenotyping and clinical trials.","volume":"28","author":"Legrand","year":"2024","journal-title":"Crit Care"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2834423\/donaldson_2025_oi_250413_1747330142.21517.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T15:00:23Z","timestamp":1748358023000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2834423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,27]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2025.12279","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,27]]}}}