The Nonlinear Impact of Cumulative Fluid Balance on Severe Acute Kidney Injury During the First Three ICU Days in Sepsis

BackgroundSepsis is a leading cause of ICU mortality, and sepsis-associated acute kidney injury (SA-AKI) significantly elevates the risk of death. This study investigated the relationship between early cumulative fluid balance and the outcomes of severe SA-AKI (SS-AKI) and 30-day mortality.MethodsData were obtained from the MIMIC-IV 3.1 database, including adult septic patients who met the Sepsis-3.0 diagnostic criteria and were admitted to the ICU for the first time between 2008 and 2019. The restricted cubic spline (RCS) model was used to analyze the nonlinear relationship between cumulative fluid balance during the first three days after ICU admission and the risk of SS-AKI. Multivariable logistic regression, Cox proportional hazards models, and propensity score matching (PSM) were employed to evaluate the effects of cumulative fluid balance on SS-AKI occurrence and 30-day mortality.ResultsAmong 2074 septic patients, 1009 (48.7%) developed SS-AKI. These patients had more severe illness and a significantly higher 3-day fluid balance. After adjusting for confounders, sensitivity analyses demonstrated a robust positive association between cumulative 3-day fluid balance and SS-AKI risk (OR = 1.043, 1.069, and 1.088), while the cumulative 3-day fluid balance was identified as a predictor of 30-day mortality (HR = 0.989, 1.003, 1.017). RCS analysis revealed a nonlinear relationship, with an inflection point at 5.21 L at Day 3. When the cumulative fluid balance exceeded this threshold, the risk of SS-AKI increased significantly. Subgroup analyses showed consistent associations across sex, age, ethnicity, diabetes status, and vasopressor use. After PSM, patients with cumulative 3-day fluid balance exceeding 5.21 L remained at significantly higher risk for SS-AKI.ConclusionsIn septic patients, cumulative fluid balance during the first three ICU days is nonlinearly associated with SS-AKI risk. When cumulative fluid balance exceeds approximately 5.21 L at Day 3, the risks of both SS-AKI and 30-day mortality increased.