Shi Chengdong, Cao Hongliang, Zeng Guoqiang, Wu Hao, Wang Yuantao
Department of Urology II, The First Hospital of Jilin University, Changchun, China.
Front Nutr. 2024 Sep 13;11:1440800. doi: 10.3389/fnut.2024.1440800. eCollection 2024.
The impact of micronutrients, including vitamins and minerals, on different kidney diseases has been reported in some observational studies; however, their causal relationship remains uncertain. We aimed to ascertain the causal genetic relationships between micronutrients and different kidney diseases using the Mendelian randomization (MR) method.
Instrumental variables (IVs) for genetically predicting calcium (Ca), iron (Ir), Zinc (Zn), selenium (Se), copper (Cu), vitamin D (Vit D), and vitamin C (Vit C) levels in humans were obtained, and a bidirectional two-sample MR was used to examine potential associations between the levels of these seven micronutrients and the risk of seven different kidney diseases including hypertensive renal disease, diabetic nephropathy, IgA nephropathy, membranous nephropathy, cystic nephropathy, chronic kidney disease (CKD), and chronic tubulo-interstitial nephritis. Five different MR analyses were conducted, with the main method being the inverse variance-weighted (IVW) method. Moreover, sensitivity analyses were performed to assess heterogeneity and potential pleiotropy.
The IVW method revealed that Ca levels were associated with a decreased risk of hypertensive renal disease (OR = 0.61, 95% CI: 0.40-0.93, -value = 0.022), and Se levels were associated with a decreased risk of hypertensive renal disease (OR = 0.72, 95% CI: 0.53-0.99, -value = 0.040), diabetic nephropathy (OR = 0.83, 95% CI: 0.73-0.93, -value = 0.002), and CKD (OR = 0.87, 95% CI: 0.77-0.99, -value = 0.028). Conversely, Vit D levels were associated with an increased risk of polycystic kidney disease (OR = 1.76, 95% CI: 1.15-2.69, -value = 0.0095). In addition, no potential causal relationship was found between vitamin C levels, iron levels, zinc levels, and copper levels and different kidney diseases. Meanwhile, inverse Mendelian randomization showed no potential causal relationship between different chronic kidney diseases and micronutrients. The Cochrane's Q test, MR-Egger regression, and MR-PRESSO did not suggest heterogeneity and pleiotropy, providing evidence of the validity of the MR estimates.
Our results indicate a cause-and-effect connection between micronutrients and certain kidney diseases, but additional study is required to provide more conclusive evidence. This research has the potential to assist clinicians in managing the consumption of specific micronutrients among individuals with chronic kidney diseases, as well as in promoting disease prevention among both healthy populations and those who are susceptible to chronic underlying conditions.
一些观察性研究报告了包括维生素和矿物质在内的微量营养素对不同肾脏疾病的影响；然而，它们之间的因果关系仍不确定。我们旨在使用孟德尔随机化（MR）方法确定微量营养素与不同肾脏疾病之间的因果遗传关系。
获取用于遗传预测人体钙（Ca）、铁（Ir）、锌（Zn）、硒（Se）、铜（Cu）、维生素D（Vit D）和维生素C（Vit C）水平的工具变量（IVs），并使用双向双样本MR来检验这七种微量营养素水平与七种不同肾脏疾病风险之间的潜在关联，这些疾病包括高血压肾病、糖尿病肾病、IgA肾病、膜性肾病、囊性肾病、慢性肾脏病（CKD）和慢性肾小管间质性肾炎。进行了五种不同的MR分析，主要方法是逆方差加权（IVW）法。此外，进行了敏感性分析以评估异质性和潜在的多效性。
IVW法显示，钙水平与高血压肾病风险降低相关（OR = 0.61，95%CI：0.40 - 0.93，P值 = 0.022），硒水平与高血压肾病风险降低相关（OR = 0.72，95%CI：0.53 - 0.99，P值 = 0.040）、糖尿病肾病（OR = 0.83，95%CI：0.73 - 0.93，P值 = 0.002）和CKD（OR = 0.87，95%CI：0.77 - 0.99，P值 = 0.028）。相反，维生素D水平与多囊肾病风险增加相关（OR = 1.76，95%CI：1.15 - 2.69，P值 = 0.0095）。此外，未发现维生素C水平、铁水平、锌水平和铜水平与不同肾脏疾病之间存在潜在因果关系。同时，反向孟德尔随机化显示不同慢性肾脏疾病与微量营养素之间无潜在因果关系。Cochrane's Q检验、MR - Egger回归和MR - PRESSO均未提示异质性和多效性，为MR估计值的有效性提供了证据。
我们的结果表明微量营养素与某些肾脏疾病之间存在因果联系，但需要更多研究提供更确凿的证据。本研究有可能帮助临床医生管理慢性肾脏病患者特定微量营养素的摄入量，以及在健康人群和易患慢性基础疾病的人群中促进疾病预防。
