Identifying acute kidney injury subphenotypes using an outcome-driven deep-learning approach.

OBJECTIVE: Acute kidney injury (AKI), a common condition on the intensive-care unit (ICU), is characterized by an abrupt decrease in kidney function within a few hours or days, leading to kidney failure or damage. Although AKI is associated with poor outcomes, current guidelines overlook the heterogeneity among patients with this condition. Identification of AKI subphenotypes could enable targeted interventions and a deeper understanding of the injury's pathophysiology. While previous approaches based on unsupervised representation learning have been used to identify AKI subphenotypes, these methods cannot assess time series or disease severity. METHODS: In this study, we developed a data- and outcome-driven deep-learning (DL) approach to identify and analyze AKI subphenotypes with prognostic and therapeutic implications. Specifically, we developed a supervised long short-term memory (LSTM) autoencoder (AE) with the aim of extracting representation from time-series EHR data that were intricately correlated with mortality. Then, subphenotypes were identified via application of K-means. RESULTS: In two publicly available datasets, three distinct clusters were identified, characterized by mortality rates of 11.3%, 17.3%, and 96.2% in one dataset and 4.6%, 12.1%, and 54.6% in the other. Further analysis demonstrated that AKI subphenotypes identified by our proposed approach were statistically significant on several clinical characteristics and outcomes. CONCLUSION: In this study, our proposed approach could successfully cluster the AKI population in ICU settings into 3 distinct subphenotypes. Thus, such approach could potentially improve outcomes of AKI patients in the ICU, with better risk assessment and potentially better personalized treatment.

A generalizable and interpretable model for mortality risk stratification of sepsis patients in intensive care unit.

PURPOSE: This study aimed to construct a mortality model for the risk stratification of intensive care unit (ICU) patients with sepsis by applying a machine learning algorithm. METHODS: Adult patients who were diagnosed with sepsis during admission to ICU were extracted from MIMIC-III, MIMIC-IV, eICU, and Zigong databases. MIMIC-III was used for model development and internal validation. The other three databases were used for external validation. Our proposed model was developed based on the Extreme Gradient Boosting (XGBoost) algorithm. The generalizability, discrimination, and validation of our model were evaluated. The Shapley Additive Explanation values were used to interpret our model and analyze the contribution of individual features. RESULTS: A total of 16,741, 15,532, 22,617, and 1,198 sepsis patients were extracted from the MIMIC-III, MIMIC-IV, eICU, and Zigong databases, respectively. The proposed model had an area under the receiver operating characteristic curve (AUROC) of 0.84 in the internal validation, which outperformed all the traditional scoring systems. In the external validations, the AUROC was 0.87 in the MIMIC-IV database, better than all the traditional scoring systems; the AUROC was 0.83 in the eICU database, higher than the Simplified Acute Physiology Score III and Sequential Organ Failure Assessment (SOFA),equal to 0.83 of the Acute Physiology and Chronic Health Evaluation IV (APACHE-IV), and the AUROC was 0.68 in the Zigong database, higher than those from the systemic inflammatory response syndrome and SOFA. Furthermore, the proposed model showed the best discriminatory and calibrated capabilities and had the best net benefit in each validation. CONCLUSIONS: The proposed algorithm based on XGBoost and SHAP-value feature selection had high performance in predicting the mortality of sepsis patients within 24 h of ICU admission.

Fine-grained subphenotypes in acute kidney injury populations based on deep clustering: Derivation and interpretation.

BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality in critically ill patients. Due to differences in the etiology and pathophysiological mechanism, the current AKI criteria put it an embarrassment to evaluate clinical therapy and prognosis. OBJECTIVE: We aimed to identify subphenotypes based on routinely collected clinical data to expose the unique pathophysiologic patterns. METHODS: A retrospective study was conducted based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD), and a deep clustering approach was conducted to derive subphenotypes. We conducted further analysis to uncover the underlying clinical patterns and interpret the subphenotype derivation. RESULTS: We studied 14,189 and 19,382 patients with AKI within 48 h of ICU admission in the two datasets, respectively. Through our approach, we identified seven distinct AKI subphenotypes with mortality heterogeneity in each cohort. These subphenotypes displayed significant variations in demographics, comorbidities, levels of laboratory measurements, and survival patterns. Notably, the subphenotypes could not be effectively characterized using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria alone. Therefore, we uncovered the unique underlying characteristics of each subphenotype through model-based interpretation. To assess the usability of the subphenotypes, we conducted an evaluation, which yielded a micro-Area Under the Receiver Operating Characteristic (AUROC) of 0.81 in the single-center cohort and 0.83 in the multi-center cohort within 48-hour of admission. CONCLUSION: We derived highly characteristic, interpretable, and usable AKI subphenotypes that exhibited superior prognostic values.