Chen Sen-Lin, Wang Zhi-Chen, Chen Geng-Zhao, Zheng Hang-Bin, Huang Sai-E
Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine Fuzhou 350003, China Key Laboratory of Rehabilitation Technology of Fujian Province Fuzhou 350003, China Fujian Provincial Key Laboratory of Cognitive Function Rehabilitation Fuzhou 350003, China Fujian University of Traditional Chinese Medicine Fuzhou 350122, China.
Fujian University of Traditional Chinese Medicine Fuzhou 350122, China.
Zhongguo Zhong Yao Za Zhi. 2025 Jun;50(12):3431-3440. doi: 10.19540/j.cnki.cjcmm.20250306.501.
Based on the traditional Chinese medicine(TCM) theory of "kidney-brain interaction", a two-sample Mendelian randomization(MR) analysis was conducted to investigate the causal effects of chronic kidney disease(CKD) on Alzheimer's disease(AD) and analyze the potential mechanisms of kidney-tonifying and essence-replenishing TCM to improve AD. From the perspective that CKD is closely related to the core pathogenesis of AD, namely "kidney deficiency, essence loss, and marrow reduction", genome-wide association study(GWAS) data was used, with the inverse variance weighting(IVW) method as the main approach to reveal the causal association between CKD and AD. Sensitivity analysis was conducted to evaluate the robustness of the results. To further investigate the causal effects of CKD on AD, two different AD datasets were used as outcomes, and the urinary albumin-to-creatinine ratio(UACR) data was used as the exposure for a supplementary analysis. On this basis, the modern scientific mechanism of the kidney-tonifying and essence-replenishing method for improving AD was further explored. The IVW analysis show that CKD(ieu-b-2: OR=1.084, 95%CI[1.011, 1.163], P=0.024; ieu-b-5067: OR=1.001, 95%CI[1.000, 1.001], P=0.002) and UACR(ieu-b-2: OR=1.247, 95%CI[1.021, 1.522], P=0.031; ieu-b-5067: OR=1.001, 95%CI[1.000, 1.003], P=0.015) both have significant causal effects on AD in different datasets, with CKD increasing the risk of AD. The sensitivity analysis further confirmed the reliability of the results. Genetic studies have shown that CKD has a significant causal effect on AD, suggesting that controlling CKD is an important intervention measure for preventing and treating AD. Therefore, further research on CKD's role in AD is crucial in clinical practice. The research enriches the theoretical implication of "kidney-brain interaction", deepens the understanding of AD' etiology, and provides further insights and directions for the prevention and treatment of AD with TCM, specifically from a kidney-based perspective.
基于中医“肾脑相关”理论，进行了两样本孟德尔随机化（MR）分析，以研究慢性肾脏病（CKD）对阿尔茨海默病（AD）的因果效应，并分析补肾填精中药改善AD的潜在机制。从CKD与AD核心病机“肾虚、精亏、髓减”密切相关的角度出发，利用全基因组关联研究（GWAS）数据，以逆方差加权（IVW）法为主要方法揭示CKD与AD之间的因果关联。进行敏感性分析以评估结果的稳健性。为进一步研究CKD对AD的因果效应，将两个不同的AD数据集作为结局，并将尿白蛋白与肌酐比值（UACR）数据作为暴露因素进行补充分析。在此基础上，进一步探索补肾填精法改善AD的现代科学机制。IVW分析表明，在不同数据集中，CKD（ieu-b-2：OR=1.084，95%CI[1.011，1.163]，P=0.024；ieu-b-5067：OR=1.001，95%CI[1.000，1.001]，P=0.002）和UACR（ieu-b-2：OR=1.247，95%CI[1.021，1.522]，P=0.031；ieu-b-5067：OR=1.001，95%CI[1.000，1.003]，P=0.015）对AD均有显著因果效应，CKD增加AD风险。敏感性分析进一步证实了结果的可靠性。遗传学研究表明，CKD对AD有显著因果效应，提示控制CKD是防治AD的重要干预措施。因此，进一步研究CKD在AD中的作用在临床实践中至关重要。该研究丰富了“肾脑相关”的理论内涵，深化了对AD病因的认识，为从肾论治AD的防治提供了进一步的思路和方向。
