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.