Association of Estimated Pulse Wave Velocity with Chronic Kidney Disease Risk: A Machine Learning Analysis Based on...

Background: Estimated pulse wave velocity (ePWV) is a non-invasive marker of arterial stiffness with potential relevance for chronic kidney disease (CKD) risk assessment. This study aimed to investigate the association between ePWV and CKD risk in the US and Chinese populations and to evaluate its discriminative performance using machine learning approaches. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES, 2005-2018, weighted n ≈ 100.9 million) and the China Health and Retirement Longitudinal Study (CHARLS, 2011-2015, n = 21,853). In NHANES, CKD was defined according to the 2021 KDIGO criteria as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g; in CHARLS, where urinary albumin was not measured, CKD was defined by the eGFR criterion alone, and this difference in case definition was taken into account when interpreting the results. Logistic regression and restricted cubic spline models were used to examine the association between ePWV and CKD, with subgroup analyses stratified by demographic and clinical characteristics. Multiple machine learning models were developed in NHANES and externally validated in CHARLS; model discrimination was assessed using the area under the receiver operating characteristic curve (AUROC), and feature importance was interpreted using SHapley Additive exPlanations (SHAP) values. Results: Higher ePWV was consistently associated with higher odds of CKD in both cohorts (NHANES: odds ratio [OR] = 1.505 per 1 m/s, 95% confidence interval [CI] = 1.459-1.552; CHARLS: OR = 1.434 per 1 m/s, 95% CI = 1.368-1.503; both p < 0.0001), with dose-response relationships observed. Formal interaction tests confirmed significant effect modification by sex (both cohorts) and by BMI and diabetes (NHANES only). Point estimates were higher in men and in NHANES obese and diabetic subgroups, but interactions across smoking and alcohol strata were not statistically significant. Among the machine learning models evaluated, discrimination was moderate and comparable across algorithms (LightGBM: AUROC = 0.804 in internal validation and 0.793 in external validation), and DeLong tests showed no significant difference between LightGBM and XGBoost (p = 0.0655 and 0.0684, respectively). SHAP analysis identified ePWV as the highest-ranking feature, surpassing uric acid, lipid levels, and diabetes history. Using the Youden index, the optimal ePWV cutoff for identifying CKD was 10.15 m/s in NHANES (sensitivity 0.658, specificity 0.695) and 10.568 m/s in CHARLS (sensitivity 0.658, specificity 0.718). Conclusions: Elevated ePWV is significantly associated with eGFR-defined CKD across the US and Chinese populations studied. These findings support ePWV as a potentially useful marker for CKD risk stratification; however, given the cross-sectional design of both cohorts, its predictive value requires confirmation in prospective studies. It is important to emphasize that no non-invasive calculated metric can replace direct measurement of serum creatinine and urinalysis for identifying individuals at risk of CKD in routine clinical practice.