Associations of clinical parameter-based accelerated aging, genetic predisposition with risk of chronic kidney disease and associated life expectancy: A prospective cohort study

Little evidence exists regarding the associations between clinical parameter-based biological aging and the incidence and outcome of chronic kidney disease (CKD). Thus, we aimed to assess the associations between biological aging, genetic risk, and the risk of CKD, as well as investigate the impact of accelerated biological aging on life expectancy. 281,363 participants free of kidney diseases from the UK Biobank were included in this prospective study. Biological age was measured from clinical traits using the KDM-BA and PhenoAge algorithms, and the discrepancies from chronological age were defined as biological age accelerations. A polygenic score was calculated to indicate the genetic predisposition of the estimated glomerular filtration rate (eGFR). A cause-specific competing risk model was used to estimate hazard ratios (HRs) and the corresponding confidence intervals (CIs) of incident CKD. We found that individuals with more pronounced accelerations in biological age exhibited an elevated risk of developing CKD (HR_{Quartile 4 vs. Quartile 1}, 1.90; 95% CI, 1.77-2.05 for KDM-BA acceleration and HR_{Quartile 4 vs. Quartile 1}, 2.79; 95% CI, 2.58-3.01 for PhenoAge acceleration), with nonlinear relationships. Notably, there were positive additive interactions between biological aging and genetic risk on CKD risk. Among the CKD population, accelerated biological aging was associated with a further decline in life expectancy. Advanced biological aging may potentially increase the vulnerability to developing CKD in individuals aged midlife and beyond, particularly among those with high genetic risk for abnormal kidney function, and could reduce the life expectancy of CKD patients.