Separating the Effects of Early-Life and Adult Body Size on Chronic Kidney Disease Risk: A Mendelian Randomization Study.

Background: Whether there is a causal relationship between childhood obesity and increased risk of chronic kidney disease (CKD) remains controversial. This study sought to explore how body size in childhood and adulthood independently affects CKD risk in later life using a Mendelian randomization (MR) approach.

Methods: Univariate and multivariate MR was used to estimate total and independent effects of body size exposures. Genetic associations with early-life and adult body size were obtained from a genome-wide association study of 453,169 participants in the U.K. Biobank, and genetic associations with CKD were obtained from the CKDGen and FinnGen consortia.

Results: A larger genetically predicted early-life body size was associated with an increased risk of CKD (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.14 to 1.41; =1.70E-05) and increased blood urea nitrogen (BUN) levels (β=0.010; 95% CI, 0.005 to 0.021; =0.001). However, the association between the impact of early-life body size on CKD (OR, 1.12; 95% CI, 0.95 to 1.31; =0.173) and BUN level (β=0.001; 95% CI, -0.010 to 0.012; =0.853) did not remain statistically significant after adjustment for adult body size. Larger genetically predicted adult body size was associated with an increased risk of CKD (OR, 1.37; 95% CI, 1.21 to 1.54; =4.60E-07), decreased estimated glomerular filtration rate (β=-0.011; 95% CI, -0.017 to -0.006; =5.79E-05), and increased BUN level (β=0.010; 95% CI, 0.002 to 0.019; =0.018).

Conclusion: Our research indicates that the significant correlation between early-life body size and CKD risk is likely due to maintaining a large body size into adulthood.