Han Qiuxia, Duan Yingjie, Jin Meiling, Ma Lijie, Zhao Xiaolin, Ren Qinqin, Chen Fei, Ding Xiaonan, Du Junxia, Song Chenwen, Xu Ke, Zhu Hanyu, Sun Qianmei
Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases, Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan-vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine, Beijing, China.
Ren Fail. 2025 Dec;47(1):2526690. doi: 10.1080/0886022X.2025.2526690. Epub 2025 Jul 23.
IgA nephropathy (IgAN) incidence is higher in gastroesophageal reflux disease (GERD) patients than those without. However, the causal link between them is unclear. This study aims to elucidate the causal relationship between GERD and IgAN through bidirectional Mendelian randomization (MR) analysis.
The chi-square test was employed to assess whether the incidence of IgAN was associated with GERD. Multivariate logistic regression was used to assess whether GERD is an independent risk factor for IgAN. Univariable and multivariable MR analyses were conducted to estimate the associations between GERD and IgAN. The MR analysis included inverse-variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods. Additionally, pleiotropy, heterogeneity, and sensitivity analyses were performed.
In two independent clinical cohorts, GERD patients showed a significantly elevated risk of IgAN. After adjusting for confounding factors such as age, gender, BMI, and hypertension, the results of multivariate logistic regression indicated that GERD is a significant risk factor for IgAN. The MR analysis demonstrated that GERD significantly increased the risk of IgAN (OR = 1.378, < 0.001). Conversely, reverse MR analysis indicated no significant increase in the risk of GERD due to IgAN. Furthermore, this study confirmed the robustness of the results, detecting no pleiotropy or heterogeneity. The multivariate MR analysis revealed that, even after adjusting for hypertension and BMI, GERD maintained a robust association with an increased risk of IgAN (OR = 1.418, < 0.001).
The study suggests that GERD increases the risk of IgAN. However, there is insufficient evidence to support reverse causality between the two diseases.
胃食管反流病（GERD）患者中IgA肾病（IgAN）的发病率高于无GERD的患者。然而，它们之间的因果关系尚不清楚。本研究旨在通过双向孟德尔随机化（MR）分析阐明GERD与IgAN之间的因果关系。
采用卡方检验评估IgAN的发病率是否与GERD相关。多元逻辑回归用于评估GERD是否为IgAN的独立危险因素。进行单变量和多变量MR分析以估计GERD与IgAN之间的关联。MR分析包括逆方差加权、MR-Egger、加权中位数、简单模式和加权模式方法。此外，还进行了多效性、异质性和敏感性分析。
在两个独立的临床队列中，GERD患者发生IgAN的风险显著升高。在调整年龄、性别、BMI和高血压等混杂因素后，多元逻辑回归结果表明GERD是IgAN的显著危险因素。MR分析表明，GERD显著增加了IgAN的风险（OR = 1.378，<0.001）。相反，反向MR分析表明，IgAN并未显著增加GERD的风险。此外，本研究证实了结果的稳健性，未发现多效性或异质性。多变量MR分析显示，即使在调整高血压和BMI后，GERD与IgAN风险增加之间仍保持稳健的关联（OR = 1.418，<0.001）。
该研究表明GERD会增加IgAN的风险。然而，没有足够的证据支持这两种疾病之间的反向因果关系。
