Early serum phosphate trajectories after acute kidney injury onset and their association with mortality in critically ill patients: derivation in MIMIC-IV and external evaluation in eICU-CRD

Abstract Background Acute kidney injury (AKI) is a common and prognostically important complication of critical illness. Although serum phosphate abnormalities have been associated with adverse outcomes, previous studies have largely focused on single measurements rather than longitudinal patterns after AKI onset. We aimed to identify distinct serum phosphate trajectories during the first 72 hours after ICU admission among critically ill patients who developed AKI within 24 hours of ICU admission and to evaluate their associations with subsequent mortality. Methods This retrospective derivation and external-evaluation study used the MIMIC-IV and eICU-CRD databases. Adults who developed AKI within 24 hours after ICU admission and had serum phosphate measurements on ICU days 1–3 were included. Group-based trajectory modeling identified phosphate trajectory patterns in MIMIC-IV. The primary outcome was 28-day mortality. A 72-hour landmark analysis separated trajectory ascertainment from subsequent mortality assessment. Associations were evaluated using Kaplan–Meier analysis, multivariable Cox regression, and subgroup analyses. The MIMIC-IV-derived model was frozen and applied to eICU-CRD without refitting. Results Among 7,894 patients in the MIMIC-IV trajectory cohort, three phosphate trajectories were identified: low-decreasing (Trajectory 1, n = 6,168; 78.1%), moderate-decreasing (Trajectory 2, n = 1,425; 18.1%), and persistently high (Trajectory 3, n = 301; 3.8%). In the 72-hour landmark cohort, compared with Trajectory 1, Trajectory 2 and Trajectory 3 remained associated with higher 28-day mortality after adjustment for age, sex, Charlson Comorbidity Index, Sequential Organ Failure Assessment (SOFA) score, and AKI stage (adjusted hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.03–1.30; P = 0.018 and adjusted HR 1.26, 95% CI 1.02–1.55; P = 0.028, respectively). In eICU-CRD, the frozen model classified 3,462 patients into the three trajectories with high classification performance. Trajectory 2 remained associated with 28-day mortality after adjustment for age, sex, and race/ethnicity (HR 1.44, 95% CI 1.13–1.83; P = 0.004). Conclusions Early serum phosphate trajectories characterize clinically distinct AKI phenotypes and are associated with subsequent mortality among critically ill patients. Further prospective studies are required to determine their clinical utility.