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

Abstract

© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.BACKGROUND: An investigation into 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 estimated glomerular filtration rate (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.