Associations of intrinsic capacity deficit proxy score and genetic susceptibility with incident chronic kidney disease and life expectancy

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. 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. 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). 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.