Effect of restrictive fluid balance in critically ill patients with acute kidney injury: a target trial emulation

PURPOSE: To estimate the effect of restrictive fluid management on renal function and mortality in critically ill patients with acute kidney injury (AKI) at high risk of developing positive fluid balance. METHODS: We conducted a target trial emulation using data from 12 intensive care units in Queensland, Australia (2015-2021). Adults with AKI within 72 h of intensive care unit (ICU) admission and an AKI-Fluid Balance Risk Score ≥ 32 were included. The intervention comprised conservative crystalloid administration, restricted nutritional fluid intake, and diuretic use for 72 h. We estimated per-protocol effects using a sequential doubly robust estimator for longitudinal modified treatment policies. The primary outcome was AKI Rank at day 7; secondary outcomes included 30-day mortality. RESULTS: Among 8,685 patients, the intervention was associated with substantial reduction in fluid balance (- 2,304 mL at 72 h; 95% CI, - 2,465 to - 2,144) and modest improvement in AKI Rank (mean difference - 0.8; 95% confidence interval (CI), - 1.3 to - 0.3). Heterogeneity by AKI stage was observed: the intervention was associated with improved renal function in stage 1 AKI (mean difference - 3.1; 95% CI, - 3.8 to - 2.5) but worse outcomes in stage 2 AKI (mean difference 4.5; 95% CI, 3.8 to 5.1) and stage 3 AKI (mean difference 6.3; 95% CI, 4.7 to 7.9) with increased 30-day mortality (relative risk 1.20; 95% CI, 1.09 to 1.33). Effective sample sizes were limited (7-16%), indicating reliance on extrapolation. CONCLUSIONS: Restrictive fluid management was associated with improved renal function in early AKI but potentially harmful effects in stages 2 and 3 AKI. These hypothesis-generating findings suggest any future trial should incorporate safety criteria for patients with advanced renal injury.

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Journal
Critical Care
Published
2026-05-30
DOI
https://doi.org/10.1186/s13054-026-06094-7
Primary Topic
Acute Kidney Injury Research
Type
article
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article

Effect of restrictive fluid balance in critically ill patients with acute kidney injury: a target trial emulation

James Walsham, Emma Williams, Hamish Pollock, Alexis Tabah et al.
Critical Care
Acute Kidney Injury Research
article

Effect of restrictive fluid balance in critically ill patients with acute kidney injury: a target trial emulation

James Walsham, Emma Williams, Hamish Pollock, Alexis Tabah, Tess Evans, Sunil Sane, Jatinder Grewal, Rod Hurford, Julia Affleck, Nermin Karamujic, Meg Harward, Siva Senthuran, Prashanti Marella, Mandy Tallott, James P. McCullough, Ra’eesa Doola, Sam Keogh, Anis Chaba, Janine Garrett, Vikram Masurkar, Neeraj Bhadange, Mahesh Ramanan, Paula Lister, George Cornmell, Wayne Stevens, Josephine Reoch, Kyle White, Lachlan Quick, Anni Paasilahti, Adam Visser, Pam Dipplesman, Cameron Anderson, Ben Nash, Dinesh Parmar, Jennifer Taylor, Langa Lutshaba, Jaco Poggenpoel, Antony Attokaran, Ahmad Nasser, Peter Garrett, Sebastiaan Blank, Zephanie Tyack, Stephen Whebell, Jayshree Lavana, Kylie Jacobs, Lauren Murray, Vikram Shah, Hannah McCabe, Ary Serpa Neto, Stephen Luke, Kerina J. Denny, Lynette Morrison, Patrick Young, Aashish Kumar, Denzil Gill, Jane Brailsford, Philippa McIlroy, Jason Meyer, Judy Smith, Kiran Shekar, Kevin B. Laupland, Felicity Edwards, Andrea Marshall, David Stewart, Jayesh Dhanani, Christopher Smart, Michelle Gatton, Sananta Dash, Vijo Kuruvilla, Stuart Baker, David Moore, Adam Suliman, Anamika Ganju, Pierre Clement
article en

Abstract

PURPOSE: To estimate the effect of restrictive fluid management on renal function and mortality in critically ill patients with acute kidney injury (AKI) at high risk of developing positive fluid balance. METHODS: We conducted a target trial emulation using data from 12 intensive care units in Queensland, Australia (2015-2021). Adults with AKI within 72 h of intensive care unit (ICU) admission and an AKI-Fluid Balance Risk Score ≥ 32 were included. The intervention comprised conservative crystalloid administration, restricted nutritional fluid intake, and diuretic use for 72 h. We estimated per-protocol effects using a sequential doubly robust estimator for longitudinal modified treatment policies. The primary outcome was AKI Rank at day 7; secondary outcomes included 30-day mortality. RESULTS: Among 8,685 patients, the intervention was associated with substantial reduction in fluid balance (- 2,304 mL at 72 h; 95% CI, - 2,465 to - 2,144) and modest improvement in AKI Rank (mean difference - 0.8; 95% confidence interval (CI), - 1.3 to - 0.3). Heterogeneity by AKI stage was observed: the intervention was associated with improved renal function in stage 1 AKI (mean difference - 3.1; 95% CI, - 3.8 to - 2.5) but worse outcomes in stage 2 AKI (mean difference 4.5; 95% CI, 3.8 to 5.1) and stage 3 AKI (mean difference 6.3; 95% CI, 4.7 to 7.9) with increased 30-day mortality (relative risk 1.20; 95% CI, 1.09 to 1.33). Effective sample sizes were limited (7-16%), indicating reliance on extrapolation. CONCLUSIONS: Restrictive fluid management was associated with improved renal function in early AKI but potentially harmful effects in stages 2 and 3 AKI. These hypothesis-generating findings suggest any future trial should incorporate safety criteria for patients with advanced renal injury.

Critical Care
Griffith University (AU), Queensland Health (AU), Queensland University of Technology (AU), The University of Queensland (AU), Royal Brisbane and Women's Hospital (AU), Gold Coast Hospital (AU), Austin Hospital (AU), Mackay Base Hospital (AU), Townsville Hospital (AU), Cairns Hospital (AU), Logan Hospital (AU), Princess Alexandra Hospital (AU), UNSW Sydney (AU), Australian and New Zealand Intensive Care Society (AU), Sunshine Coast University Hospital (AU), The George Institute for Global Health (AU), Prince Charles Hospital (AU), Redcliffe Hospital (AU), Monash University (AU), Central Queensland University (AU), James Cook University (AU)
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Acute Kidney Injury Research
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