| Title: | Association between intrinsic capacity and incident chronic kidney disease: The mediating role of metabolomic signatures |
| Journal: | Maturitas |
| Published: | 2 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42235097/ |
| DOI: | https://doi.org/10.1016/j.maturitas.2026.109007 |
Publication 19793
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Abstract
BACKGROUND: The relationship between intrinsic capacity and incident chronic kidney disease and its underlying mechanisms are unknown. This study investigated this relationship and assessed the potential role of metabolic mechanisms.</p>
METHODS: We included 431,208 UK Biobank participants without baseline chronic kidney disease. An intrinsic capacity deficit score was computed from 7 factors across 4 intrinsic capacity domains. Cox proportional hazard regression was used to investigate the association between intrinsic capacity deficit score and incident chronic kidney disease. Elastic net regression determined the metabolic signature associated with intrinsic capacity deficit score. Mediation analysis assessed the mediating role of metabolic signature and specific metabolites.</p>
RESULTS: During a median follow-up of 13.9 years, 19,264 incident chronic kidney disease cases were identified. Compared with participants with an intrinsic capacity deficit score of 0, those with a score of 4+ exhibited a significantly elevated risk of chronic kidney disease (HR 1.49, 95% CI 1.40-1.59). We identified 43 metabolites related to intrinsic capacity deficit score (17 positively, 26 negatively). The metabolic signature partly mediated the association between intrinsic capacity deficit score and risk of chronic kidney disease (proportion of mediation effects 4.10%, 95% CI 2.67-5.92). Significant mediation effects were also observed for metabolites related to lipid metabolism, fatty acids, and amino acids, with PM% ranging from 0.13 to 1.78.</p>
CONCLUSIONS: Higher intrinsic capacity deficit score was associated with an elevated risk of chronic kidney disease. This relationship was partially mediated through perturbations in metabolic profiles-particularly those involving lipid-related metabolites, fatty acids, and amino acids.</p>
9 Authors
- Chunlei Li
- Mingdan Xu
- Shuo Lu
- Yuqing Yan
- Xiangying Suo
- Jintao Han
- Hua Ye
- Yacong Bo
- Quanjun Lyu
1 Application
| Application ID | Title |
|---|---|
| 93398 | Investigating the risk factors of non-communicable chronic disease using biomarkers, lifestyle factors, and environmental factors |
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