Abstract
Obesity is reported as closely correlated with the development of chronic kidney disease (CKD); however, whether causation exists is unknown, and controversy remains about whether the role of obesity is protective or destructive in CKD. In this study, we attempted to infer the causal relationship between life course adiposity and CKD, to provide a rationale for obesity management in CKD patients. A 2-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship of life course adiposity traits 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 the outcome. The causal relationship was evaluated by inverse variance weighted, MR Egger regression and weighted median methods, and further verified by extensive sensitivity analyses. Genetically determined one standard deviation increase in adult BMI was associated with higher risk of CKD in all 4 MR methods. Other indexes including childhood BMI, body fat percentage, and waist/hip circumference were also shown to have a causal effect on the risk of CKD. The results were robust under all sensitivity analyses. There exists a causal effect of life course adiposity on the risk of CKD. A genetic predisposition to higher adult BMI may increase the risk of CKD.
Highlights
Chronic kidney disease (CKD) is a global public health problem, characterized by persistent alterations in kidney structure and function [1]
Results of Mendelian randomization (MR) analysis showed that each one standard deviation (1-SD) increase in body mass index (BMI) was associated with higher risk of CKD consistently in 4 methods, including inverse variance weighted (IVW) [odds ratio (OR): 1.214, 95% confidence interval (CI): 1.115–1.321, P=7.9E−06), MR Egger (OR: 1.245, 95% CI: 1.011– 1.533, P=4.2E−02), weighted mode (OR: 1.448, 95% CI: 1.202–1.745, P=2.1E−04), and weighted median (OR: 1.336, 95% CI: 1.184–1.508, P=2.7E−06) (Figure 1)
A 1-SD increase in childhood BMI was associated with higher risk of CKD at nominal significant level in IVW method (OR: 1.166, 95% CI: 1.056–1.286, P=2.3E−03)
Summary
Chronic kidney disease (CKD) is a global public health problem, characterized by persistent alterations in kidney structure and function [1]. Studies have demonstrated that increased waist-to-hip ratio (WHR) increase the risk of CKD mortality [8] These population-based studies have reported a positive association between obesity/adiposity and CKD, conflicting evidence has shown that obesity was paradoxically associated with greater survival following the onset of CKD [9,10]. Two pervious studies investigated the causal association between CKD and obesity traits including BMI and WHR from a genetic perspective [12,13], but no systematic analysis has been conducted to investigate the life course adiposity and CKD. Methods: A 2-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship of life course adiposity traits 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. A genetic predisposition to higher adult BMI may increase the risk of CKD
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