| Title: | Associations of intrinsic capacity deficit proxy score and genetic susceptibility with incident chronic kidney disease and life expectancy |
| Journal: | The Journals of Gerontology Series A |
| Published: | 5 Oct 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41105198/ |
| DOI: | https://doi.org/10.1093/gerona/glaf187 |
Publication 19289
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Abstract
BACKGROUND: Intrinsic capacity (IC), reflecting an individual's physical and mental capacities, is a core concept proposed by the World Health Organization (WHO) to promote healthy aging. This study aimed at examining the association between IC and chronic kidney disease (CKD) incidence and outcomes.</p>
METHODS: We analyzed 389 805 UK Biobank participants without baseline CKD. Functional decline was quantified using an IC deficit proxy score derived from eight biomarkers across five IC domains. A polygenic score (PGS) for estimated glomerular filtration rate (eGFR) was also calculated. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CKD, and two-sample Mendelian randomization (MR) was conducted to explore potential causal relationships.</p>
RESULTS: A one-point increment in the IC deficit proxy score was associated with a higher risk of developing CKD (HR = 1.16, 95% CI, 1.14, 1.18; P-trend < .0001), independent of genetic susceptibility to eGFR. The highest risk of CKD was observed among individuals with a high IC deficit and low genetically predicted eGFR (HR = 1.88, 95% CI, 1.72-2.06). MR analysis supported a causal relationship between faster walking pace and lower CKD risk. Among individuals with CKD, a higher IC deficit proxy score (3+) was linked to reduced life expectancy at age 45 years (1.09 years lost in life expectancy; 95% CI, 0.68-1.51).</p>
CONCLUSIONS: IC decline was independently associated with increased CKD risk and with further reductions in life expectancy. Enhancing IC may be a viable strategy for CKD prevention and healthy aging.</p>
14 Keywords
- Aged
- Female
- Genetic Predisposition to Disease
- Glomerular Filtration Rate
- Humans
- Incidence
- Life Expectancy
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Proportional Hazards Models
- Renal Insufficiency, Chronic
- Risk Factors
- United Kingdom
10 Authors
- Gang Zheng
- Fengrong Ou
- Shuxian Chen
- Chao Ji
- Qing Chang
- Difei Wang
- Honghao Yang
- Zheng Ma
- Yang Xia
- Yuhong Zhao
1 Application
| Application ID | Title |
|---|---|
| 524293 | The Role of Nutrition and Healthy Lifestyles in Metabolic, Cardiovascular, and Aging-Related Diseases: Impacts on Healthy Aging |
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