Relationship between birth weight and chronic kidney disease: an integrative analysis of observational studies and causal inference through genetic approaches

ObjectiveAlthough many observational studies have shown that there was an inverse association between birth weight and chronic kidney disease (CKD) in adults, whether such association is causal remains largely unclear.\n\nMethodsWe first conducted a systematic review and meta-analysis to investigate the association between birth weight and CKD. Then using a set of valid instrumental variables for birth weight, we performed a two-sample Mendelian randomization (MR) to evaluate its causal effect on CKD based on summary association statistics available from large scale genome-wide association study (GWAS) (up to 143,677 individuals for birth weight and 118,147 individuals for CKD). We further validated the MR results with extensive sensitive analyses.\n\nResultsThe results of meta-analysis showed that individuals with low birth weight have about 76% (95% CI 36[~]126%) higher risk of CKD in late life compared with those with normal birth weight. Depending on 26 instrumental variables, the inverse variance weighted MR showed that the odds ratio per one SD increase of birth weight on CKD was estimated to be 0.91 (95% CI 0.72[~]1.14, p=0.396). The similar null association between birth weight and CKD is also observed using the weighted median method and maximum likelihood method as well as the Egger regression. Such non-significant association is robust against potential instrumental outliers and pleiotropic effects.\n\nConclusionOur study identifies an inverse association between birth weight and adult CKD in observational studies, while it is not supportive of the causal role of birth weight on CKD based on our MR analysis.