Development and validation of an inflammatory index-based interpretable machine learning model for mortality risk...

Hemodialysis patients with end-stage renal disease have high all-cause mortality, with chronic low-grade inflammation as a key prognostic factor. Existing mortality prediction models lack both accuracy and clinical interpretability, and no studies have systematically integrated multiple inflammatory indices (neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, etc.) into interpretable tools for this population.

A single-center retrospective cohort study included 512 hemodialysis patients (Jan 2021-Oct 2024) from The Central Hospital of Wuhan, split into training (70%), validation (15%), and test (15%) sets per TRIPOD guidelines. Fifteen baseline clinical variables and five inflammatory indices were collected. Missing data were imputed, data normalized, and oversampling used to address imbalance. Twelve models (9 traditional machine learning, 1 neural network, 2 ensembles) were built, optimized via tenfold cross validation, and interpreted with SHapley Additive exPlanations.

At follow-up (Oct 30, 2024), 212 (41.4%) patients died. Non-survivors differed significantly from survivors in myocardial infarction (16.0% vs. 2.7%, p < 0.001), neutrophil-to-lymphocyte ratio (median: 4.1 vs. 3.6, p = 0.012), dialysis vintage (42.5 vs. 77.5 months, p < 0.001), and age (62.2 ± 12.3 vs. 58.1 ± 13.3 years, p < 0.001). The Stacking model performed best (AUC = 0.983, accuracy = 0.922), outperforming logistic regression (AUC = 0.703). Body mass index, myocardial infarction history, and neutrophil-to-lymphocyte ratio were top predictors.

The interpretable stacking model enables accurate mortality risk stratification for hemodialysis patients. Future multi-center validation and multi-modal data integration will enhance its generalizability for clinical application.