BackgroundSepsis-associated acute kidney injury (S-AKI) is a major contributor to mortality in intensive care units (ICU). Early prediction of mortality risk is crucial to enhance prognosis and optimize clinical decisions. This study aims to develop a 28-day mortality risk prediction model for S-AKI utilizing an explainable ensemble machine learning (ML) algorithm.MethodsThis study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV 2.0) database to gather information on patients with S-AKI. Univariate regression, correlation analysis and Boruta were combined for feature selection. To construct the four ML models, hyperparameters were tuned via random search and five-fold cross-validation. To evaluate the performance of all models, ROC, K-S, and LIFT curves were used. The discrimination of ML models and traditional scoring systems was compared using area under the receiver operating characteristic curve (AUC). Additionally, the SHapley Additive exPlanation (SHAP) was utilized to interpret the ML model and identify essential variables. To investigate the relationship between the top nine continuous variables and the risk of 28-day mortality. COX regression-restricted cubic splines were utilized while controlling for age and comorbidities.ResultsThe study analyzed data from 9,158 patients with S-AKI, dividing them into a 28-day mortality group of 1,940 and a survival group of 7,578. The results showed that XGBoost was the best performing model of the four ML models with AUC of 0.873. All models outperformed APS-III 0.713 and SAPS-II 0.681. The K-S and LIFT curves indicated XGBoost as the most effective predictor for 28-day mortality risk. The model’s performance was evaluated using ROCpr curves, calibration curves, accuracy, precision, and F1 scores. SHAP force plots were utilized to interpret and visualize the personalized predictive power of the 28-day mortality risk model. Additionally, COX regression restricted cubic splines revealed an interesting non-linear relationship between the top nine variables and 28-day mortality.ConclusionThe use of ensemble ML models has shown to be more effective than the LR model and conventional scoring systems in predicting 28-day mortality risk in S-AKI patients. By visualizing the XGBoost model with the best predictive performance, clinicians are able to identify high-risk patients early on and improve prognosis.