Association of Life-Course Stressful Life Events with Incident Chronic Kidney Disease: The Potential Mediating Role of Frailty

Background/Objectives: Our research sought to explore the association between life-course stressful life events (SLEs) and incident chronic kidney disease (CKD) in middle-aged and older Chinese adults, as well as to examine frailty as a potential mediating pathway. Methods: We performed a prospective cohort study utilizing information from the 2011–2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). SLEs were retrospectively assessed for childhood and adulthood. We utilized multivariable logistic regression models to determine the association between life-course SLEs and incident CKD. Subgroup analyses and interaction effects were used to detect possible differences across clinical and demographic subgroups. Mediation analyses were conducted to examine frailty’s role as a potential mediating pathway. Various sensitivity analyses were executed to test the primary outcomes’ stability. Results: In total, 3358 subjects were analyzed in the final study. During a 4-year follow-up, 241 individuals were detected with incident CKD. The fully adjusted model indicated that individuals who experienced SLE exposure were associated with higher odds of incident CKD than those who did not (OR = 2.05, 95% CI: 1.44–2.91, p < 0.001). When subjects were divided into four mutually exclusive SLE exposure patterns, those exposed to SLEs during both childhood and adulthood had the highest odds of incident CKD compared with those unexposed during either life stage (OR = 2.52, 95% CI: 1.66–3.81, p < 0.001), followed by those exposed only during adulthood (OR = 1.95, 95% CI: 1.30–2.93, p = 0.001) and those exposed only in childhood (OR = 1.83, 95% CI: 1.21–2.78, p = 0.004). The predefined subgroups exhibited no statistically significant interaction effects. Mediation analyses revealed that frailty statistically accounted for approximately 12% of the observed association between SLE exposure and incident CKD. Conclusions: Experiencing life-course SLEs was associated with higher odds of developing CKD in middle-aged and older Chinese adults. Frailty may represent one potential mediating pathway linking life-course SLEs with incident CKD. These results underscore the significance of considering life-course psychosocial stress and frailty when identifying individuals potentially vulnerable to CKD.