Cumulative metabolic syndrome components, inflammation, and chronic kidney disease: associations, mediation pathways and joint effects
4 affiliations
- 1Department of General Practice and International Medical Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- 2Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine
- 3Department of Cardiovascular Medicine, Shanghai Institute of Hypertension, National Center for Translational Medicine, Shanghai, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension
- 4Computer Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Abstract
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.
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BibTeX
@article{jiang2026cumulative,
title = {{Cumulative metabolic syndrome components, inflammation, and chronic kidney disease: associations, mediation pathways and joint effects}},
author = {Yiya Jiang and Ling-Meng Wang and Kaiyu Cai and Zi-Long Lu and Yiran Jiang and Jianren Que and Wei Shao and Chang-Sheng Sheng and Hua Yan and Tingwei Su},
journal = {Frontiers in Endocrinology},
year = {2026},
month = nov,
doi = {10.3389/fendo.2026.1991493},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1991493/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cumulative metabolic syndrome components, inflammation, and chronic kidney disease: associations, mediation pathways and joint effects
AU - Yiya Jiang
AU - Ling-Meng Wang
AU - Kaiyu Cai
AU - Zi-Long Lu
AU - Yiran Jiang
AU - Jianren Que
AU - Wei Shao
AU - Chang-Sheng Sheng
AU - Hua Yan
AU - Tingwei Su
PY - 2026
DA - 2026/11/05
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1991493
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1991493/full
AB - 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.
SN - 1664-2392
ER -