Acute kidney injury prediction for non-critical care patients: a retrospective external and internal validation study

Background: Acute kidney injury (AKI), the decline of kidney excretory function, occurs in up to 18% of hospitalized admissions. Progression of AKI may lead to irreversible kidney damage. Methods: This retrospective cohort study includes adult patients admitted to a non-intensive care unit at the University of Pittsburgh Medical Center (UPMC) (n = 46,815) and University of Florida Health (UFH) (n = 127,202). We developed and compared deep learning and conventional machine learning models to predict progression to Stage 2 or higher AKI within the next 48 hours. We trained local models for each site (UFH Model trained on UFH, UPMC Model trained on UPMC) and a separate model with a development cohort of patients from both sites (UFH-UPMC Model). We internally and externally validated the models on each site and performed subgroup analyses across sex and race. Results: Stage 2 or higher AKI occurred in 3% (n=3,257) and 8% (n=2,296) of UFH and UPMC patients, respectively. Area under the receiver operating curve values (AUROC) for the UFH test cohort ranged between 0.77 (UPMC Model) and 0.81 (UFH Model), while AUROC values ranged between 0.79 (UFH Model) and 0.83 (UPMC Model) for the UPMC test cohort. UFH-UPMC Model achieved an AUROC of 0.81 (95% confidence interval [CI] [0.80, 0.83]) for UFH and 0.82 (95% CI [0.81,0.84]) for UPMC test cohorts; an area under the precision recall curve values (AUPRC) of 0.6 (95% CI, [0.05, 0.06]) for UFH and 0.13 (95% CI, [0.11,0.15]) for UPMC test cohorts. Kinetic estimated glomerular filtration rate, nephrotoxic drug burden and blood urea nitrogen remained the top three features with the highest influence across the models and health centers. Conclusion: Locally developed models displayed marginally reduced discrimination when tested on another institution, while the top set of influencing features remained the same across the models and sites.

Identifying acute illness phenotypes via deep temporal interpolation and clustering network on physiologic signatures

Initial hours of hospital admission impact clinical trajectory, but early clinical decisions often suffer due to data paucity. With clustering analysis for vital signs within six hours of admission, patient phenotypes with distinct pathophysiological signatures and outcomes may support early clinical decisions. We created a single-center, longitudinal EHR dataset for 75,762 adults admitted to a tertiary care center for 6+ hours. We proposed a deep temporal interpolation and clustering network to extract latent representations from sparse, irregularly sampled vital sign data and derived distinct patient phenotypes in a training cohort (n=41,502). Model and hyper-parameters were chosen based on a validation cohort (n=17,415). Test cohort (n=16,845) was used to analyze reproducibility and correlation with biomarkers. The training, validation, and testing cohorts had similar distributions of age (54-55 yrs), sex (55% female), race, comorbidities, and illness severity. Four clusters were identified. Phenotype A (18%) had most comorbid disease with higher rate of prolonged respiratory insufficiency, acute kidney injury, sepsis, and three-year mortality. Phenotypes B (33%) and C (31%) had diffuse patterns of mild organ dysfunction. Phenotype B had favorable short-term outcomes but second-highest three-year mortality. Phenotype C had favorable clinical outcomes. Phenotype D (17%) had early/persistent hypotension, high rate of early surgery, and substantial biomarker rate of inflammation but second-lowest three-year mortality. After comparing phenotypes' SOFA scores, clustering results did not simply repeat other acuity assessments. In a heterogeneous cohort, four phenotypes with distinct categories of disease and outcomes were identified by a deep temporal interpolation and clustering network. This tool may impact triage decisions and clinical decision-support under time constraints.

Clinical Courses of Acute Kidney Injury in Hospitalized Patients: A Multistate Analysis

Objectives: We aim to quantify longitudinal acute kidney injury (AKI) trajectories and to describe transitions through progressing and recovery states and outcomes among hospitalized patients using multistate models. Methods: In this large, longitudinal cohort study, 138,449 adult patients admitted to a quaternary care hospital between 2012 and 2019 were staged based on Kidney Disease: Improving Global Outcomes serum creatinine criteria for the first 14 days of their hospital stay. We fit multistate models to estimate probability of being in a certain clinical state at a given time after entering each one of the AKI stages. We investigated the effects of selected variables on transition rates via Cox proportional hazards regression models. Results: Twenty percent of hospitalized encounters (49,325/246,964) had AKI; among patients with AKI, 66% had Stage 1 AKI, 18% had Stage 2 AKI, and 17% had AKI Stage 3 with or without RRT. At seven days following Stage 1 AKI, 69% (95% confidence interval [CI]: 68.8%-70.5%) were either resolved to No AKI or discharged, while smaller proportions of recovery (26.8%, 95% CI: 26.1%-27.5%) and discharge (17.4%, 95% CI: 16.8%-18.0%) were observed following AKI Stage 2. At 14 days following Stage 1 AKI, patients with more frail conditions (Charlson comorbidity index greater than or equal to 3 and had prolonged ICU stay) had lower proportion of transitioning to No AKI or discharge states. Discussion: Multistate analyses showed that the majority of Stage 2 and higher severity AKI patients could not resolve within seven days; therefore, strategies preventing the persistence or progression of AKI would contribute to the patients' life quality. Conclusions: We demonstrate multistate modeling framework's utility as a mechanism for a better understanding of the clinical course of AKI with the potential to facilitate treatment and resource planning.