Remnant cholesterol, preinflammatory state and chronic kidney disease: association and mediation analyses

Abstract

Blood lipid management is a key approach in the prevention of chronic kidney disease (CKD). Remnant cholesterol (RC) plays an important role in the development of multiple diseases via chronic inflammation. The aim of our study was to determine the relationship between RC and CKD and explore the role of inflammation in this relationship. The 7696 subjects from the Chinese Health and Nutrition Survey were divided into four subgroups according to the quartile of RC. The estimated glomerular filtration rate was calculated using the CKD Epidemiology Collaboration equation. Fasting RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Logistic regression analysis was employed to evaluate the relationships between RC and CKD. Mediation analysis was undertaken to identify potential mediators of high-sensitivity C-reactive protein (hs-CRP) and white blood cells (WBCs). Of all participants, the mean age was 51 years, and the male accounted for 47.8%. The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 1.40 (1.10–1.78, p for trend = 0.006) for CKD. RC and preinflammatory markers have combined effect on CKD. The preinflammatory state, presented by increased hs-CRP or WBCs, partially mediated the association between RC and CKD with proportion of 10.14% (p = 0.002) and 11.65% (p = 0.012), respectively. In conclusion, this study suggested a positive relationship between RC and CKD, which was partially mediated by preinflammatory state. These findings highlight the importance of RC and inflammation in renal dysfunction.

IMPACT STATEMENT

• What is already known on this subject?: Dyslipidemia plays an important role in the development of chronic kidney disease (CKD). Remnant cholesterol (RC), as a triglyceride-rich particle, can contribute to target organ damage, primarily through inflammatory pathways. However, the relationship between RC and CKD in the community-dwelling population, particularly the role of inflammation, is not yet fully understood.

• What do the results of this study add?: This study shows that RC was significantly associated with CKD. RC and preinflammatory status exhibit a combined effect on CKD. Preinflammatory state, presented by increased high-sensitivity C-reactive protein or white blood cells, partially mediated the association between RC and CKD.

• What are the implications of these findings for clinical practice and/or further research?: The study provides us with a better understanding of the role of RC and inflammation in kidney dysfunction and raises the awareness of RC in the management of CKD.

Keywords:

• Chronic kidney disease
• inflammation
• mediation
• remnant cholesterol

Acknowledgments

We would like to thank the Chinese Health and Nutrition Survey research team, the field team, and every respondent for their time and efforts that they have devoted to the Chinese Health and Nutrition Survey project.

Ethical approval

Study protocols and ethics approval were derived from the Institutional Review Committees of the University of North Carolina at Chapel Hill and the National Institute for Nutrition and Health at Beijing and were attributed to the two centers. Each participant in our study was enrolled in China and assigned the informed consent.

Author contributions

YG Yuan, XM Hu, SH Zhang, WM Wang, BY Yu, YQ Ou, YL Zhou, and HJ Dong contributed to the study conception and design. YG Yuan, XM Hu, SH Zhang, WM Wang, and BY Yu collected and analyzed the data, and interpreted the results. YG Yuan and XM Hu drafted the manuscript and prepared tables and figures. SH Zhang, WM Wang, BY Yu, YQ Ou, YL Zhou, and HJ Dong revised the manuscript for important intellectual content. YQ Ou, YL Zhou, and HJ Dong provided study supervision and funding.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data in this study are available at: https://www.cpc.unc.edu/projects/china.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 82373529), the Department of Science and Technology of Guangdong Province, China (No. 2024A1515012943 and No. 2020B1111170011), and the Science and Technology Project of Tibet Autonomous Region (No. XZ202201ZY0051G).