Abstract
Although chronic kidney disease (CKD) is associated with obesity, few studies have used visceral adipose tissue (VAT) as an indicator to investigate its causal effect on CKD. Therefore, Mendelian randomization (MR) was employed to study the causal effects of VAT on CKD and its potential mediation by hypertension. Genome-wide association study (GWAS) statistics on VAT exposure were obtained from the UK Biobank, while GWAS datasets of CKD outcomes were obtained from CKDGen and FinnGen (validation study). Furthermore, VAT was considered the exposure, with the estimated glomerular filtration rate based on creatinine (eGFR (crea)), estimated glomerular filtration rate based on cystatin C (eGFR(cys)), and blood urea nitrogen (BUN) employed to assess the causal effect of VAT on kidney test indicators. Lastly, a two-step MR method was used to study the mediating role of hypertension in the pathogenesis of VAT among patients with CKD. VAT exhibited a positive causal association with CKD, irrespective of whether the GWAS datasets from CKDGen (odds ratio [OR] = 1.18, 95% CI: 1.08 to 1.29, P = 1.433140e-04) or FinnGen (1.47, 1.30 to 1.67, p = 2.500000e-09). VAT was not causally associated with eGFR (crea) (1.00, 0.99 to 1.00, p = 0.53), was negatively associated with eGFR (cys) (0.95, 0.93 to 0.97, P = 5.070000e-10), and was positively associated with BUN (1.02,1.01 to 1.02, P = 7.824860e-04). The mediating effect of VAT on CKD via hypertension was 45.8% (95% CI: 26.4 65.1). VAT has a positive causal effect on CKD, with hypertension playing a significant role. However, the effects of VAT on renal function indicators require further investigation.