Gao Teng-Yu, Wang Jun-Chi, Zhao Qi-Jian, Zhou Xiang-Ning, Jiang Yu-Ting, Ren Lian, Zhang Chao
Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Obes Rev. 2025 Feb;26(2):e13845. doi: 10.1111/obr.13845. Epub 2024 Oct 10.
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.
尽管慢性肾脏病（CKD）与肥胖相关，但很少有研究使用内脏脂肪组织（VAT）作为指标来研究其对CKD的因果效应。因此，采用孟德尔随机化（MR）方法来研究VAT对CKD的因果效应及其通过高血压的潜在中介作用。关于VAT暴露的全基因组关联研究（GWAS）统计数据来自英国生物银行，而CKD结局的GWAS数据集来自CKDGen和FinnGen（验证研究）。此外，将VAT视为暴露因素，使用基于肌酐的估计肾小球滤过率（eGFR（crea））、基于胱抑素C的估计肾小球滤过率（eGFR（cys））和血尿素氮（BUN）来评估VAT对肾脏检测指标的因果效应。最后，采用两步MR方法研究高血压在CKD患者VAT发病机制中的中介作用。无论来自CKDGen（优势比[OR]=1.18，95%可信区间：1.08至1.29，P=1.433140×10⁻⁴）还是FinnGen（1.47，1.30至1.67，p=2.500000×10⁻⁹）的GWAS数据集，VAT均与CKD呈正因果关联。VAT与eGFR（crea）无因果关联（1.00，0.99至1.00，p=0.53），与eGFR（cys）呈负相关（0.95，0.93至0.97，P=5.070000×10⁻¹⁰），与BUN呈正相关（1.02，1.01至1.02，P=7.824860×10⁻⁴）。VAT通过高血压对CKD的中介效应为45.8%（95%可信区间：26.4至65.1）。VAT对CKD有正向因果效应，高血压起重要作用。然而，VAT对肾功能指标的影响需要进一步研究。
