Causal effects of physical activity or sedentary behaviors on kidney function: an integrated population-scale observational analysis and Mendelian randomization study.

Background An investigation for the causality of the effects of physical activity and specific sedentary activities on kidney function in the general population is warranted. Methods In this observational cohort study, first, the clinical associations of the prevalence of stages 3-5 chronic kidney disease (CKD) and the eGFR with physical activity, determined by self-report or objective wrist-band accelerometer results, and sedentary activities (watching television, using a computer, and driving) were investigated in 329,758 UK Biobank participants. To assess causality, a two-sample Mendelian randomization (MR) analysis was performed to investigate the associations of a genetic predisposition to physical activity and a sedentary lifestyle with the risk of kidney function impairment in an independent CKDGen genome-wide association study (N = 567,460). The findings were replicated with the 321,024 UK white British Biobank participants in the allele-score-based one-sample MR. Results A higher degree of self-reported or accelerometer-determined moderate-to-vigorous physical activity was associated with a higher eGFR, while a longer time spent watching television was significantly associated with a lower eGFR and a higher prevalence of CKD. The two-sample MR demonstrated that the genetic predisposition to a higher degree of physical activity was associated with a lower risk of CKD and a higher eGFR, while the genetically predicted television watching duration was associated with a higher risk of CKD and a lower eGFR. The other sedentary behaviors yielded inconsistent results. The findings were similarly replicated in the one-sample MR. Conclusion Physical activity and television watching causally affect kidney function in the general population.