Wang Chenxin, Li Yanran, Zhong Linyu, Sun Na, Luo Denggui, Xu Yuanzhao, Qi Airong
The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
Medicine (Baltimore). 2025 Jul 25;104(30):e43353. doi: 10.1097/MD.0000000000043353.
IgA nephropathy (IgAN) is the leading cause of end-stage renal disease, although its mechanisms remain incompletely understood. Previous studies have identified metabolites associated with IgAN, but their causal relationships require further investigation. This study employed a 2-sample Mendelian randomization (MR) approach to assess the causal relationships between 1400 serum metabolites and IgAN. Causal effects between these metabolites and IgAN were estimated using the inverse-variance weighted method. Additional analyses, including MR-Egger regression, weighted median, simple mode, and weighted mode methods, were conducted to refine and validate these findings. Pleiotropy and heterogeneity tests were also performed. The initial analysis identified 9 known and 4 novel metabolites associated with IgAN. Notably, Acisoga was found to increase the risk of IgAN, whereas serine exhibited a protective effect; both findings were confirmed by robust statistical tests (P < .05). This initial MR analysis highlights 2 metabolites significantly linked to IgAN, providing valuable insights into the disease' s underlying mechanisms for clinical research. Further investigation is needed to validate these findings.
IgA肾病（IgAN）是终末期肾病的主要病因，尽管其发病机制仍未完全明确。既往研究已鉴定出与IgA肾病相关的代谢物，但其因果关系仍需进一步研究。本研究采用两样本孟德尔随机化（MR）方法，评估1400种血清代谢物与IgA肾病之间的因果关系。使用逆方差加权法估计这些代谢物与IgA肾病之间的因果效应。还进行了包括MR-Egger回归、加权中位数、简单模式和加权模式方法在内的额外分析，以完善和验证这些发现。同时进行了多效性和异质性检验。初步分析确定了9种已知和4种新的与IgA肾病相关的代谢物。值得注意的是，发现阿西索加会增加IgA肾病的风险，而丝氨酸则具有保护作用；这两个发现均通过可靠的统计学检验得到证实（P < 0.05）。这项初步的MR分析突出了2种与IgA肾病显著相关的代谢物，为临床研究中该疾病的潜在机制提供了有价值的见解。需要进一步研究来验证这些发现。
