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

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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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