A machine learning model for diabetic retinopathy risk stratification using routine blood and urine parameters: insights into kidney-eye crosstalk.

Objective: This study aimed to develop and externally validate an interpretable machine learning (ML) model for diabetic retinopathy (DR) risk stratification using routine clinical biomarkers, and to explore potential probabilistic dependencies and interactive pathways between clinical biomarkers and DR pathogenesis through Bayesian network modeling. Methods: We integrated clinical data from the National Health and Nutrition Examination Survey (NHANES) with an independent hospital cohort (Nantong First People's Hospital). A multi-stage feature selection pipeline (Boruta algorithm and LASSO regression) was utilized to identify core predictors. Eight ML algorithms were benchmarked. To transcend conventional "black-box" predictions, we coupled SHAP (SHapley Additive exPlanations) for personalized interpretability with a Bayesian Network Directed Acyclic Graph (DAG) to map the probabilistic dependency structure among the selected systemic biomarkers. Results: The LightGBM algorithm outperformed other classifiers, yielding a robust external validation AUC of 0.841 (95% CI: 0.809-0.862). Fourteen key routine predictors were identified, spanning glycemic control, renal function, and lipid metabolism. Crucially, probabilistic dependency structure via the Bayesian Network revealed a hierarchical pathogenetic topology: rather than parallel associations, latent renal impairment markers (urine protein, BUN, and urine creatinine) and chronic glycemic toxicity (HbA1c) emerged as direct upstream dependency drivers of DR. This structural evidence suggests a probabilistic dependency consistent with the 'kidney-eye crosstalk' hypothesis. Conclusion: We successfully deployed a high-performing, non-invasive LightGBM model for early DR screening. By integrating predictive ML with probabilistic dependency structure, this framework not only delivers an accessible, web-based clinical decision support system (CDSS) for resource-constrained settings but also provides preliminary insights into the potential systemic microvascular interplay driving diabetic retinopathy.