AKI-twinX: explainable organ structured digital twin for sepsis AKI trajectory forecasting.

Acute kidney injury in sepsis evolves over hours to days, yet most ICU models emphasize onset and provide limited insight into cardio-renal interactions. We developed AKI-twinX, an organ-structured, explainable digital twin that jointly forecasts acute kidney injury onset, acute kidney injury trajectory, and near-term mortality risk. The model learns renal and cardiovascular latent states with sparse feature gating and captures cross-organ coupling with attention. We trained AKI-twinX on MIMIC-IV sepsis using 5-fold cross-validation and evaluated it on an Indiana University Health cohort. Discrimination was consistent across systems (AUC: mortality 0.86-0.88, acute kidney injury onset 0.78-0.82, acute kidney injury trajectory 0.73-0.78). In vasopressor-treated windows, 12-hour systolic blood pressure forecasts tracked observed values (mean absolute error 8.5 mmHg). Counterfactual vasopressor withdrawal shifted predicted blood pressure downward and increased predicted risk, supporting sensitivity to clinically meaningful interventions. AKI-twinX enables trajectory-aware forecasting with bedside auditability in sepsis.