Association of blood urea nitrogen to high-density lipoprotein ratio with all-cause and cardiovascular mortality in individuals with mildly reduced eGFR.

BACKGROUND: Patients with mild-to-moderate renal impairment face elevated cardiovascular risk, yet early detection tools remain limited. The Cardiovascular-Kidney-Metabolism (CKM) interplay underscores the need for integrated biomarkers. The Blood Urea Nitrogen (BUN) to High-Density Lipoprotein (HDL) cholesterol ratio (BUN/HDL) was therefore evaluated for early risk stratification. METHODS: This cohort study included National Health and Nutrition Examination Survey (NHANES) participants (2007‒2018) with mildly reduced estimated Glomerular Filtration Rate ([eGFR] < 90 mL/min/1.73 m2). Associations of BUN/HDL with all-cause and cardiovascular mortality was examined using survey-weighted multivariable Cox regression. The Boruta algorithm with Adaptive Best Subset Selection (ABESS) identified optimal predictor sets. Model performance was quantified by discrimination (AUC) and calibration (Brier score and calibration slope). Incremental value was assessed using net reclassification improvement (NRI) and Integrated Discrimination Improvement (IDI). RESULTS: Elevated BUN/HDL showed a modest association with all-cause (HR = 1.050, 95% CI: 1.021-1.081) and cardiovascular mortality (HR = 1.062, 95% CI: 1.020‒1.105). Optimal cut-points were 6.41 (AUC = 0.650) for all-cause and 5.00 (AUC = 0.682) for cardiovascular mortality. Subgroup analyses suggested a stage-dependent pattern. For all-cause mortality, associations were consistent in Chronic Kidney Disease (CKD) stage G2 (HR = 1.079, p = 0.002) and G3 (HR = 1.058, p = 0.025). For cardiovascular mortality, the association was significant in CKD stage G2 (HR = 1.127, p < 0.001). This cardiovascular association was stronger in non-hypertensive individuals. Machine learning confirmed BUN/HDL as a robust predictor within NHANES dataset, with final models showing excellent discrimination (AUCs 0.820-0.837) and calibration. CONCLUSION: The BUN/HDL ratio demonstrates a consistent, albeit modest, association with mid-term mortality, providing preliminary support as a CKM risk indicator among individuals with mildly reduced eGFR.