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Randomized Controlled Trial
. 2025 May 1;8(5):e2512279.
doi: 10.1001/jamanetworkopen.2025.12279.

Hydrocortisone and Risk Factors for Kidney Replacement Therapy in Septic Shock

Lachlan H Donaldson  1   2   3 , Anthony Devaux  1 , Kyle C White  4   5 , Dorrilyn Rajbhandari  1 , Jeremy Cohen  1   6   7 , Rinaldo Bellomo  8   9   10 , John Myburgh  1   11 , Naomi Hammond  1   2 , Balasubramanian Venkatesh  1   12
Affiliations
Randomized Controlled Trial

Hydrocortisone and Risk Factors for Kidney Replacement Therapy in Septic Shock

Lachlan H Donaldson et al. JAMA Netw Open. .

Abstract

Importance: 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.

Objective: 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]).

Design, setting, and participants: 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.

Exposures: 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.

Main outcomes and measures: Outcomes of interest were KRT requirement and liberation from KRT, measured as days alive and free of KRT.

Results: 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 = .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 = .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, -4.31 to 6.87] days; P = .65).

Conclusions and relevance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Cohen reported receiving grants from the National Health and Medical Research Council (NHMRC) during the conduct of the study. Dr Myburgh reported receiving grants from the George Institute for Global Health Project from NHMRC during the conduct of the study. Dr Venkatesh reported receiving grants from NHMRC (paid to institution) during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Selection and Outcome of Participants in Cohort
ADRENAL indicates Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock; KRT, kidney replacement therapy.
Figure 2.
Figure 2.. Outcomes for Patients With Kidney Replacement Therapy (KRT) Requirement
By approximately day 30, few patients were weaned off KRT and remained alive.
See this image and copyright information in PMC

Comment in

  • doi: 10.1001/jamanetworkopen.2025.12286

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