In utero, childhood, and adolescence tobacco smoke exposure, physical activity, and chronic kidney disease incidence in adulthood: evidence from a large prospective cohort study

The adverse effects of early-life tobacco smoke exposure on chronic kidney disease (CKD) risk remain unclear. This study aimed to investigate the associations of early-life tobacco smoke exposure with CKD incidence in adulthood, and further explore the modification effects of physical activity (PA). A total of 352,883 participants were included from the UK Biobank. The information on early-life tobacco smoke exposure was assessed by employing in utero tobacco smoke exposure and age of smoking initiation. Weekly moderate-to-vigorous physical activity (MVPA) was calculated for each individual. Cox proportional hazard regression was fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI) of CKD risk, and to investigate the modification effects of MVPA. CKD incidence significantly increased in participants with in utero tobacco smoke exposure (HR: 1.08, 95% CI: 1.04, 1.12). Compared with never-smokers, we found a monotonic increase in the risk of CKD with smoking initiation across adulthood (HR: 1.21, 95% CI: 1.16, 1.27), adolescence (HR: 1.29, 95% CI: 1.24, 1.35), and childhood (HR: 1.34, 95% CI: 1.25, 1.43) (P trend < 0.001). Additionally, we identified joint cumulative effects of MVPA and early-life tobacco smoke exposure on incident CKD. Compared with never-smokers with recommended MVPA, prenatal or childhood tobacco smokers without recommended MVPA had the highest CKD risk, and the HRs (95% CIs) were 1.17 (1.10, 1.24) and 1.51 (1.36, 1.68), respectively. Early-life tobacco smoke exposure may contribute to CKD incidence in adulthood, and the observed associations could be modified by MVPA. These findings provide important information on CKD prevention in the participant’s early life while urging a more rapid and powerful need for tobacco control among pregnant couples, children, and adolescents.