| Title: | Causal Effect of Kidney Function on Lipid Metabolism: An Integrated Population-Scale Observational Analysis and Mendelian Randomization Study |
| Journal: | Kidney Medicine |
| Published: | 1 Jan 2026 |
| DOI: | https://doi.org/10.1016/j.xkme.2026.101245 |
| URL: | http://dx.doi.org/10.1016/j.xkme.2026.101245 |
Publication 16934
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Abstract
Rationale & Objective Additional investigations into the causal effects of kidney function on various metabolites, particularly lipoprotein lipids in detailed subfractions of lipoprotein particles, in the general population are warranted. Study Design The integrated cross-sectional observational and Mendelian randomization (MR) analyses. Setting & Participants We included 157,541 participants aged 40-69 years from the UK Biobank study, a population-scale prospective cohort. Genetic instruments for estimated glomerular filtration rate (eGFR) were developed from the Chronic Kidney Disease Genetics genome-wide association study meta-analysis results, which comprised 567,460 individuals of European ancestry. Exposure EGFR for observational analysis and genetically predicted eGFR for MR analysis. Outcomes Each of the 178 metabolites from recently updated metabolomics data, including detailed lipoprotein components within 14 subclasses of lipoprotein particles. Analytical Approach Observational analysis was performed using multivariate linear regression adjusted for various clinicodemographic characteristics. A two-sample MR analysis was performed using the random-effects inverse variance weighted method as the main MR method. Results In the integrated results of the observational and MR analyses, 25 metabolites were causally associated with eGFR. A lower eGFR causally decreased lipoprotein components of high-density lipoprotein and several of its subclasses, particularly medium-sized high-density lipoprotein. Conversely, a lower eGFR causally increased triglycerides levels in smaller-sized very-low-density lipoprotein and intermediate-density lipoprotein, as well as increased lipoprotein particle concentrations and total lipids in small very-low-density lipoprotein. Additionally, a lower eGFR causally increased the ratio of monounsaturated fatty acids to total fatty acids, and that of apolipoprotein B to apolipoprotein A-1. Limitations Possibility of false-negative findings when integrating observational and MR analyses. Conclusions Decreased kidney function causally aggravates lipoprotein lipid profiles; therefore, clinicians should closely monitor the lipid profiles of individuals with impaired kidney function.</p>
17 Authors
- Minsang Kim
- Jung Hun Koh
- Seong Geun Kim
- Soojin Lee
- Yaerim Kim
- Jeong Min Cho
- Semin Cho
- Kwangsoo Kim
- Yong Chul Kim
- Seung Seok Han
- Hajeong Lee
- Jung Pyo Lee
- Kwon Wook Joo
- Chun Soo Lim
- Yon Su Kim
- Dong Ki Kim
- Sehoon Park
1 Application
| Application ID | Title |
|---|---|
| 53799 | Impact of genetic and environmental factors on the health-related outcomes in chronic kidney disease patients |
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