中国血液净化

中国血液净化 ›› 2026, Vol. 25 ›› Issue (04): 310-315.doi: 10.3969/j.issn.1671-4091.2026.04.008

• 临床研究 • 上一篇    下一篇

虚弱介导慢性肾脏病与四肢瘦体质量的因果关系——孟德尔随机化研究

马晨红    张玉彩    姚书格    李翠霞    张丽君    郭云岭   

  1. 054002 邢台，邢台医学高等专科学校第二附属医院1消毒供应中心2肾内科 3放射科 4中医科
  • 收稿日期:2025-06-05 修回日期:2025-12-15 出版日期:2026-04-12 发布日期:2026-04-12
  • 通讯作者: 马晨红 E-mail:shugeyao008@163.com
  • 基金资助:
    邢台市重点研发计划(2021ZC181)

Frailty mediates the causal relationship between chronic kidney disease and appendicular lean mass: a Mendelian randomization study

MA Chen-hong, ZHANG Yu-cai, YAO Shu-ge, LI Cui-xia, ZHANG Li-jun, GUO Yun-ling#br#   

  1. Sterile Supply Center, 2Department of Nephrology, 3Department of Radiology, and 4Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Xingtai Medical College, Xingtai 054002, China
  • Received:2025-06-05 Revised:2025-12-15 Online:2026-04-12 Published:2026-04-12
  • Contact: 054002 邢台，邢台医学高等专科学校第二附属医院1消毒供应中心 E-mail:shugeyao008@163.com

摘要： 目的  探究虚弱指数(frailty Index；FI)、水肿和抑郁在慢性肾脏病(chronic kidney disease，CKD)患者中对四肢瘦体质量(appendicular lean mass，ALM)的基因因果关系，为CKD相关肌肉减少症的预防提供依据。 方法  基于公开的全基因组关联研究(genome-wide association studies，GWAS)数据库，提取与FI、水肿、抑郁、CKD及ALM相关的全基因组关联(genome-wide association study，GWAS)摘要数据。首先，采用两步法孟德尔随机化(two-step Mendelian randomization, Two-step MR)确定CKD与ALM之间可能的中介因子。随后，通过多变量孟德尔随机化(multivariable Mendelian randomization,MVMR)分析，筛选出与ALM独立相关的因果变量。最后，构建中介MR模型，将CKD设为暴露因素，ALM设为结局变量，以显著的独立因果变量作为中介，探讨潜在的中介路径。 结果  经Two-step MR、MVMR及中介MR分析，结果显示FI为CKD与ALM之间的潜在独立中介因子(OR=0.458，95% CI:0.411～0.511，P=0.021)。进一步分析表明，CKD通过FI对ALM存在显著的中介因果作用(β中介效应量=-0.24，OR=0.787，95% CI:0.67～0.978，P=0.019)。 结论  CKD对ALM的影响主要经虚弱状态间接实现，虚弱是CKD相关肌肉减少症的重要中介因素，为临床干预提供遗传机制依据。

关键词: 慢性肾脏病, 虚弱, 水肿, 抑郁, 四肢瘦体质量, 两步法孟德尔随机化, 多变量孟德尔随机化, 中介孟德尔随机化

Abstract: Objective To investigate frailty index (FI), edema, and depression in the genetic causal relationship between chronic kidney disease (CKD) and appendicular lean mass (ALM), in order to provide references for the prevention of CKD-related sarcopenia.  Methods  Summary data for FI, edema, depression, CKD, and ALM were obtained from publicly available genome-wide association study (GWAS) databases. A two-step Mendelian randomization (MR) approach was first applied to evaluate potential mediators between CKD and ALM. Subsequently, multivariable Mendelian randomization (MVMR) analysis was conducted to identify causal factors independently associated with ALM. Finally, a mediation MR model was constructed, with CKD as the exposure, ALM as the outcome, and the identified independent causal factors as mediators to explore potential mediation pathways.  Results  Two-step MR, MVMR, and mediation MR analyses revealed that FI is a potential independent mediator between CKD and ALM (OR=0.458, 95% CI: 0.411～0.511, P=0.021). Further mediation analysis indicated a significant indirect causal effect of CKD on ALM through FI (βmediation effect=-0.24, OR=0.787, 95% CI: 0.67～0.978, P=0.019).  Conclusion  The effect of CKD on ALM is primarily mediated indirectly through frailty. Frailty serves as a key mediator of CKD-related sarcopenia, providing a genetic basis for clinical intervention of sarcopenia.

Key words: Chronic kidney disease, Frailty, Edema, Depression, Appendicular lean mass, Two-step Mendelian randomization, Multivariable Mendelian randomization, Mediation Mendelian randomization

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