Liu Minghui, Wu Jian, Gao Meng, Li Yongchao, Xia Weiping, Zhang Youjie, Chen Jinbo, Chen Zhiyong, Zhu Zewu, Chen Hequn
Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Front Endocrinol (Lausanne). 2023 Sep 22;14:1240171. doi: 10.3389/fendo.2023.1240171. eCollection 2023.
The early identification of modifiable risk factors is important for preventing kidney stones but determining causal associations can be difficult with epidemiological data. We aimed to genetically assess the causality between modifiable factors (lifestyle factors, serum parameters, and metabolic comorbidities) and the risk of kidney stones. Additionally, we aimed to explore the causal impact of education on kidney stones and its potential mediating pathways.
We conducted a two-sample Mendelian randomization (MR) study to explore the causal association between 44 modifiable risk factors and kidney stones. The FinnGen dataset initially explored the causal relationship of risk factors with kidney stones and the UK Biobank dataset was used as the validation set. Then, a meta-analysis was conducted by combining discovery and validation datasets. We used two-step MR to assess potential mediators and their mediation proportions between education and kidney stones.
The combined results indicated that previous exposures may increase the risk of kidney stones, including sedentary behavior, urinary sodium, the urinary sodium/potassium ratio, the urinary sodium/creatinine ratio, serum calcium, 25-hydroxyvitamin D (25OHD), the estimated creatinine-based glomerular filtration rate (eGFRcrea), GFR estimated by serum cystatin C (eGFRcys), body mass index (BMI), waist circumference, type 2 diabetes mellitus (T2DM), fasting insulin, glycated hemoglobin, and hypertension. Coffee intake, plasma caffeine levels, educational attainment, and the urinary potassium/creatinine ratio may decrease the risk of kidney stones. Ranked by mediation proportion, the effect of education on the risk of kidney stones was mediated by five modifiable risk factors, including sedentary behavior (mediation proportion, 25.7%), smoking initiation (10.2%), BMI (8.2%), T2DM (5.8%), and waist circumference (3.2%).
This study provides MR evidence supporting causal associations of many modifiable risk factors with kidney stones. Sedentary lifestyles, obesity, smoking, and T2DM are mediating factors in the causal relationship between educational attainment and kidney stones. Our results suggest more attention should be paid to these modifiable factors to prevent kidney stones.
早期识别可改变的风险因素对于预防肾结石很重要，但利用流行病学数据确定因果关联可能具有挑战性。我们旨在通过基因评估可改变因素（生活方式因素、血清参数和代谢合并症）与肾结石风险之间的因果关系。此外，我们旨在探讨教育对肾结石的因果影响及其潜在的中介途径。
我们进行了一项两样本孟德尔随机化（MR）研究，以探讨44种可改变的风险因素与肾结石之间的因果关联。FinnGen数据集最初探索了风险因素与肾结石的因果关系，英国生物银行数据集用作验证集。然后，通过合并发现数据集和验证数据集进行荟萃分析。我们使用两步MR来评估教育与肾结石之间潜在的中介因素及其中介比例。
综合结果表明，既往暴露可能会增加肾结石风险，包括久坐行为、尿钠、尿钠/钾比值、尿钠/肌酐比值、血清钙、25-羟维生素D（25OHD）、基于肌酐估计的肾小球滤过率（eGFRcrea）、血清胱抑素C估计的肾小球滤过率（eGFRcys）、体重指数（BMI）、腰围、2型糖尿病（T2DM）、空腹胰岛素、糖化血红蛋白和高血压。咖啡摄入量、血浆咖啡因水平、受教育程度和尿钾/肌酐比值可能会降低肾结石风险。按中介比例排序，教育对肾结石风险的影响由五个可改变的风险因素介导，包括久坐行为（中介比例为25.7%）、开始吸烟（10.2%）、BMI（8.2%）、T2DM（5.8%）和腰围（3.2%）。
本研究提供了MR证据，支持许多可改变的风险因素与肾结石之间的因果关联。久坐的生活方式、肥胖、吸烟和T2DM是受教育程度与肾结石之间因果关系的中介因素。我们的结果表明，应更多地关注这些可改变的因素以预防肾结石。
