Cumulative metabolic syndrome components, inflammation, and chronic kidney disease: associations, mediation pathways and joint effects

Objectives Metabolic syndrome (MetS) and chronic kidney disease (CKD) are major health burdens, but the pathways linking cumulative MetS burden to CKD, especially via inflammation, remain unclear. This study investigated the associations of individual MetS components and their cumulative number with CKD, the mediating roles of pan-immune-inflammation value (PIV) and C-reactive protein (CRP), and the joint effects of these markers and the number of MetS components on CKD. Methods Cross-sectional data were analyzed from 20,326 adults in Shanghai (2019–2025). MetS was defined by modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria, with body mass index (BMI) substituting waist. Multivariable regression and mediation analyses were performed; PIV = neutrophil × platelet × monocyte/lymphocyte. Results Covariate-adjusted, each MetS component was significantly associated with CKD (odds ratios [ORs]: 1.21–2.04); elevated blood pressure and fasting glucose showed strongest associations. Sex-stratified analyses showed attenuated association for triglycerides in men (OR=1.16), while obesity and low high-density lipoprotein (HDL) were non-significant in women (OR=1.42 and 0.88). A clear dose-response was observed: ORs increased from 1.39 (one component) to 6.00 (≥4). PIV and CRP partially mediated this, but the proportions were small (≤9.0%) and declined with MetS burden (1.7% for ≥4). Joint analyses showed participants with high inflammatory markers and multiple components had the highest CKD risk (OR=8.93), no significant interaction. Conclusions Cumulative MetS burden shows dose-response association with CKD, partially mediated by PIV and CRP. Concurrent elevation of metabolic burden and inflammation identifies substantially higher CKD risk, supporting combined assessment for stratification.