Causality of visceral adipose tissue on chronic kidney disease and renal function measure indicators, and mediation role of hypertension: Mendelian randomization study.

IF 8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Obesity Reviews Pub Date : 2024-10-10 DOI:10.1111/obr.13845
Teng-Yu Gao, Jun-Chi Wang, Qi-Jian Zhao, Xiang-Ning Zhou, Yu-Ting Jiang, Lian Ren, Chao Zhang
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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.

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内脏脂肪组织对慢性肾脏病和肾功能测量指标的因果关系及高血压的中介作用:孟德尔随机研究
虽然慢性肾脏病(CKD)与肥胖有关,但很少有研究使用内脏脂肪组织(VAT)作为指标来研究其对慢性肾脏病的因果效应。因此,研究人员采用孟德尔随机法(MR)研究了内脏脂肪组织对 CKD 的因果效应及其与高血压的潜在中介作用。有关增值税暴露的全基因组关联研究(GWAS)统计数据来自英国生物库,而有关 CKD 结果的 GWAS 数据集来自 CKDGen 和 FinnGen(验证研究)。此外,将增值税视为暴露,并采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)来评估增值税对肾脏检测指标的因果效应。最后,采用两步磁共振法研究了高血压在 CKD 患者 VAT 发病机制中的中介作用。无论 GWAS 数据集是来自 CKDGen(几率比 [OR] = 1.18,95% CI:1.08 至 1.29,P = 1.433140e-04)还是 FinnGen(1.47,1.30 至 1.67,P = 2.500000e-09),VAT 都与 CKD 呈正因果关系。VAT 与 eGFR(crea)(1.00,0.99 至 1.00,P = 0.53)无因果关系,与 eGFR(cys)呈负相关(0.95,0.93 至 0.97,P = 5.070000e-10),与 BUN 呈正相关(1.02,1.01 至 1.02,P = 7.824860e-04)。VAT 通过高血压对 CKD 的中介效应为 45.8%(95% CI:26.4 65.1)。VAT 对 CKD 具有积极的因果效应,高血压在其中发挥了重要作用。然而,增值税对肾功能指标的影响还需要进一步研究。
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来源期刊
Obesity Reviews
Obesity Reviews 医学-内分泌学与代谢
CiteScore
19.30
自引率
1.10%
发文量
130
审稿时长
1 months
期刊介绍: Obesity Reviews is a monthly journal publishing reviews on all disciplines related to obesity and its comorbidities. This includes basic and behavioral sciences, clinical treatment and outcomes, epidemiology, prevention and public health. The journal should, therefore, appeal to all professionals with an interest in obesity and its comorbidities. Review types may include systematic narrative reviews, quantitative meta-analyses and narrative reviews but all must offer new insights, critical or novel perspectives that will enhance the state of knowledge in the field. The editorial policy is to publish high quality peer-reviewed manuscripts that provide needed new insight into all aspects of obesity and its related comorbidities while minimizing the period between submission and publication.
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