Joint effects of physical activity and depressive symptoms on chronic kidney disease risk: Findings from the CHARLS cohort.

INTRODUCTION: Physical inactivity and depressive symptoms are established risk factors for chronic kidney disease (CKD), but their joint effects on incident CKD remain unclear. This study investigates the independent and joint associations of physical activity and depressive symptoms with incident CKD in middle-aged and older adults. METHODS: This study used data from the China Health and Retirement Longitudinal Study (CHARLS), with baseline data collected between 2011 and 2012 and follow-up through 2018. A total of 1599 participants without CKD at baseline were included. Participants were categorized into 4 groups based on physical activity levels (active vs inactive) and depressive symptoms (yes vs none) at baseline. Incident CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73m2 or self-reported physician diagnosis during follow-up. Association between physical activity, depressive symptoms, and CKD were explored using Cox proportional hazards models. Additive interaction was estimated using the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). RESULTS: During a median follow-up of 9.0 years, 345 (21.6%) participants developed CKD (incidence rate per 1000 person-years: 26.93). Compared with physically active participants without depressive symptoms, the adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for incident CKD were 1.22 (95% CI: 0.82, 1.83) for physical inactivity without depressive symptoms, 1.67 (95% CI: 1.29, 2.15) for physically active with depressive symptoms, and 2.21 (95% CI: 1.51, 3.23) for physical inactivity with depressive symptoms, after adjusting for potential confounders. Additive interaction estimates suggested a sub-additive joint association between physical inactivity and depressive symptoms (RERI = -0.77, 95% CI: -1.77, 0.24; AP = -0.70, 95% CI: -1.34, -0.05; SI = 0.55, 95% CI: 0.09, 1.01). However, this finding should be interpreted cautiously because the confidence intervals for the RERI and SI included their respective null values. CONCLUSIONS: The combination of physical inactivity and depressive symptoms significantly associated with incident CKD in middle-aged and older adults. These findings suggest that physical inactivity and depressive symptoms should be considered jointly in CKD risk assessment. Whether interventions targeting these factors can reduce CKD incidence requires evaluation in future intervention studies.