Zhu Xiaoli, Wu Qin
Department of Nephrology, Beijing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central Hospital, 97 South Renmin Road, Shunqing District, Nanchong, 637000, Sichuan, China.
Clin Exp Nephrol. 2025 Aug 18. doi: 10.1007/s10157-025-02752-2.
This study aims to investigate the bidirectional causal relationship between chronic kidney disease (CKD) and sarcopenia using two-sample Mendelian randomization (MR) analysis.
A bidirectional MR analysis was performed using genetic data for CKD from the MEGASTROKE consortium and sarcopenia traits from the UK Biobank. SNPs associated with CKD and sarcopenia were used as instrumental variables. MR analysis was conducted with inverse variance weighting (IVW), weighted median, and MR-Egger methods. Sensitivity analyses included Cochran's Q test, MR-Egger intercept, and the leave-one-out method. Enrichment analysis was performed using GO and KEGG pathways.
The results indicate a positive association between CKD and both left-hand grip strength (OR = 1.03, 95% CI 1.01-1.04, P < 0.001) and right-hand grip strength (OR = 1.03, 95% CI 1.02-1.04, P < 0.001) for both sides. In addition, appendicular lean mass (ALM) was found to be positively associated with an increased risk of CKD (OR = 1.35, 95% CI 1.19-1.53, P < 0.001). However, no significant causal relationships were observed between CKD and ALM or usual walking pace. Enrichment analysis identified several relevant biological processes and pathways, such as DNA transcription regulation, protein degradation, and immune response pathways, that may mediate the relationship between CKD and sarcopenia.
This study provides evidence for a bidirectional causal relationship between CKD and sarcopenia, with CKD contributing to decreased hand grip strength and ALM being associated with an increased risk of CKD.
本研究旨在使用两样本孟德尔随机化（MR）分析来探究慢性肾脏病（CKD）与肌肉减少症之间的双向因果关系。
使用来自MEGASTROKE联盟的CKD遗传数据和来自英国生物银行的肌肉减少症特征进行双向MR分析。与CKD和肌肉减少症相关的单核苷酸多态性（SNP）用作工具变量。采用逆方差加权（IVW）、加权中位数和MR-Egger方法进行MR分析。敏感性分析包括Cochran's Q检验、MR-Egger截距和留一法。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路进行富集分析。
结果表明，CKD与双侧左手握力（比值比[OR]=1.03，95%置信区间[CI]1.01-1.04，P<0.001）和右手握力（OR=1.03，95%CI 1.02-1.04，P<0.001）均呈正相关。此外，发现四肢瘦体重（ALM）与CKD风险增加呈正相关（OR=1.35，95%CI 1.19-1.53，P<0.001）。然而，未观察到CKD与ALM或日常步行速度之间存在显著因果关系。富集分析确定了几个相关的生物学过程和通路，如DNA转录调控、蛋白质降解和免疫反应通路，这些可能介导CKD与肌肉减少症之间的关系。
本研究为CKD与肌肉减少症之间的双向因果关系提供了证据，CKD导致握力下降，而ALM与CKD风险增加相关。
