Hypertension and diabetes, but not leptin and adiponectin, mediate the relationship between body fat and chronic kidney disease

Purpose: Obesity may promote kidney damage through hemodynamic and hormonal effects. We investigated the association between body mass index (BMI), total body fat (TBF) and chronic kidney disease (CKD) and whether hypertension, diabetes, leptin and adiponectin mediated these associations. Methods: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, 6671 participants (45–65 y) were included. We defined CKD as eGFR <60 ml/min/1.73 m²and/or moderately increased albuminuria. The percentage of mediation was calculated using general structural equation modeling, adjusted for potential confounding factors age, sex, smoking, ethnicity, physical activity and Dutch healthy diet index. Results: At baseline mean (SD) age was 56 (6), BMI 26.3 (4.4), 44% men, and 4% had CKD. Higher BMI and TBF were associated with 1.08 (95%CI 1.05; 1.11) and 1.05-fold (95%CI 1.02; 1.08) increased odds of CKD, respectively. As adiponectin was not associated with any of the outcomes, it was not studied further as a mediating factor. The association between BMI and CKD was 8.5% (95%CI 0.5; 16.5) mediated by diabetes and 22.3% (95%CI 7.5; 37.2) by hypertension. In addition, the association between TBF and CKD was 9.6% (95%CI −0.4; 19.6) mediated by diabetes and 22.4% (95%CI 4.2; 40.6) by hypertension. We could not confirm mediation by leptin in the association between BMI and CKD (35.6% [95%CI −18.8; 90.3]), nor between TBF and CKD (59.7% [95%CI −7.1; 126.6]). Conclusion: Our results suggest that the relations between BMI, TBF and CKD are in part mediated by diabetes and hypertension.