Causal effects of obesity on estimated glomerular filtration rate: a Mendelian randomization and image data analysis study.

Background: Obesity has been associated with onset and progression of chronic kidney disease (CKD) but causal relationship remains uncertain. This study investigated how obesity causally affects estimated glomerular filtration rate.

Methods: Cross-sectional and magnetic resonance imaging (MRI) data analyses were performed within the Prospective Investigation of Obesity, Energy, and Metabolism (POEM) study (502 participants, all aged 50 years). Additionally Mendelian randomization was performed using published summary data. Outcomes were creatinine- and cystatin C-based eGFR. Body mass index (BMI) and waist circumference (WC) were used as exposure variables in the cross-sectional and Mendelian randomization analyses. In the imaging data analyses, eGFR was regressed non-parametrically on tissue volume for each 3D voxel and visualized as a correlation "Imiomics" map.

Results: Negative correlations were shown between cystatin C-based eGFR and BMI [beta = -0.190 (95% CI: -0.280 to -0.100)] and WC [beta = -0.160 (95% CI: -0.250 to -0.060)] in an adjusted model. In contrast, a positive association was found for creatinine-based eGFR [BMI beta = 1.20 (95% CI: 0.030 to 0.210) and WC beta = 0.160 (95% CI: 0.070 to 0.260)]. Similar patterns were found using MRI analysis (Imiomics map). Mendelian randomization implied a negative causal effect of obesity-related measures on cystatin C-based eGFR [BMI beta = -0.031 (95% CI: -0.037 to -0.026) and WC beta = -0.038 (95% CI: -0.045 to -0.031)], but no statistically significant effect was found for creatinine-based eGFR.

Conclusion: This study suggests a causal negative effect of obesity on cystatin C-based, but not creatinine-based eGFR. These findings warrant further research regarding estimations of kidney function when assessing obesity and CKD.