Causal Effects of Life Course Adiposity on Chronic Kidney Disease: A Mendelian Randomization Study

Abstract

Background Obesity is reported to be tightly correlated the development of chronic kidney disease (CKD). However, whether there exists causation is unknown, and it remains controversial about the role of obesity in CKD is protective or destructive. In this study, we try to infer the causal relationship between life course adiposity and CKD, to provide a rationale for obesity management in CKD patients.Methods A two-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship of life course adiposity traits including including body mass index (BMI), childhood BMI, body fat percentage (BF), birth weight (BW), waist circumference, hip circumference and waist-to-hip ratio (WHR) to CKD. Significant single nucleotide polymorphisms from genome-wide association study on human adiposity traits were utilized as exposure instruments, and summary statistics of CKD as outcome. The causal relationship was evaluated by inverse variance weighted, MR Egger regression and weighted median methods, and further verified by extensive sensitivity analyses.Results Genetically determined one standard deviation increase in adult BMI was associated with higher risk of CKD in all four MR methods. And other indexes including childhood BMI, body fat percentage, and waist/hip circumference also have a causal effect on the risk of CKD. The results were robust under all sensitivity analyses.Conclusions There exist causal effect of life course adiposity on the risk of CKD. A genetic predisposition to higher adult BMI may increase the risk of CKD.