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. 2021 Jan;32(1):127-137.
doi: 10.1681/ASN.2020050679. Epub 2020 Oct 30.

Conventional and Genetic Evidence on the Association between Adiposity and CKD

Pengfei Zhu  1   2 , William G Herrington  1   2   3 , Richard Haynes  1   2   3 , Jonathan Emberson  1   2   4 , Martin J Landray  1   2   4   5   6 , Cathie L M Sudlow  7 , Mark Woodward  8   9   10 , Colin Baigent  1   2 , Sarah Lewington  2 , Natalie Staplin  1   2   4
Affiliations

Conventional and Genetic Evidence on the Association between Adiposity and CKD

Pengfei Zhu et al. J Am Soc Nephrol. 2021 Jan.

Abstract

Background: The size of any causal contribution of central and general adiposity to CKD risk and the underlying mechanism of mediation are unknown.

Methods: Data from 281,228 UK Biobank participants were used to estimate the relevance of waist-to-hip ratio and body mass index (BMI) to CKD prevalence. Conventional approaches used logistic regression. Genetic analyses used Mendelian randomization (MR) and data from 394 waist-to-hip ratio and 773 BMI-associated loci. Models assessed the role of known mediators (diabetes mellitus and BP) by adjusting for measured values (conventional analyses) or genetic associations of the selected loci (multivariable MR).

Results: Evidence of CKD was found in 18,034 (6.4%) participants. Each 0.06 higher measured waist-to-hip ratio and each 5-kg/m2 increase in BMI were associated with 69% (odds ratio, 1.69; 95% CI, 1.64 to 1.74) and 58% (1.58; 1.55 to 1.62) higher odds of CKD, respectively. In analogous MR analyses, each 0.06-genetically-predicted higher waist-to-hip ratio was associated with a 29% (1.29; 1.20 to 1.38) increased odds of CKD, and each 5-kg/m2 genetically-predicted higher BMI was associated with a 49% (1.49; 1.39 to 1.59) increased odds. After adjusting for diabetes and measured BP, chi-squared values for associations for waist-to-hip ratio and BMI fell by 56%. In contrast, mediator adjustment using multivariable MR found 83% and 69% reductions in chi-squared values for genetically-predicted waist-to-hip ratio and BMI models, respectively.

Conclusions: Genetic analyses suggest that conventional associations between central and general adiposity with CKD are largely causal. However, conventional approaches underestimate mediating roles of diabetes, BP, and their correlates. Genetic approaches suggest these mediators explain most of adiposity-CKD-associated risk.

Keywords: Mendelian randomization; body mass index; central adiposity; chronic kidney disease; epidemiology and outcomes; obesity.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
High waist-to-hip ratio and BMI are independent moderate “causal” risk factors for CKD. Figure 1 shows conventional and genetic associations between adiposity measures and CKD.
See this image and copyright information in PMC

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