Wang Peixi, Shang Huifang, Li Chunyu
Department of Neurology, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China.
Outpatient Department, West China Hospital, Sichuan University, Chengdu, China.
Neurol Sci. 2025 Jul 11. doi: 10.1007/s10072-025-08361-x.
Multiple evidence has suggested interaction between neurodegenerative disorders (NDDs) and creatinine, a metabolite derived from the high-energy product creatine. However, findings across studies have shown inconsistency, and the effect direction remains controversial. Here, we aimed to explore the link between creatinine and the risk of NDDs.
Utilizing data from the UK Biobank, we investigated the association between baseline serum and urine creatinine and the risk of common NDDs using Cox proportional hazards regression analysis. Furthermore, we performed genetic correlation and Mendelian randomization analyses based on summary statistics from genome-wide association studies.
A higher level of serum creatinine at baseline was associated with a lower risk of incident amyotrophic lateral sclerosis (ALS) (beta=-0.013, SE = 0.004, P = 1.88E-03). From the genetic perspective, a significant and negative genetic correlation was identified between serum creatinine and ALS risk (genetic correlation: -0.17, P = 0.017). Mendelian randomization analysis corroborated the primary finding, indicating that serum creatinine was associated with a reduced risk of ALS (OR: 0.92, 95% CI: 0.86-0.98, P = 0.01). Moreover, a higher level of baseline serum creatinine was associated with a reduced risk of incident Alzheimer's disease (beta=-4.89E-03, SE = 2.24E-03, P = 0.03), though the effect size was small.
These findings enhance our understanding of creatinine's role in the risk of NDDS, suggest the potential of targeting creatinine as a biomarker of ALS, and hold implications for designing therapeutic interventions in clinical trials.
多项证据表明神经退行性疾病（NDDs）与肌酐（一种由高能产物肌酸衍生而来的代谢物）之间存在相互作用。然而，各项研究的结果并不一致，其影响方向仍存在争议。在此，我们旨在探讨肌酐与NDDs风险之间的联系。
利用英国生物银行的数据，我们采用Cox比例风险回归分析，研究了基线血清和尿肌酐与常见NDDs风险之间的关联。此外，我们基于全基因组关联研究的汇总统计数据进行了遗传相关性和孟德尔随机化分析。
基线血清肌酐水平较高与肌萎缩侧索硬化症（ALS）发病风险较低相关（β=-0.013，标准误=0.004，P=1.88E-03）。从遗传学角度来看，血清肌酐与ALS风险之间存在显著的负遗传相关性（遗传相关性：-0.17, P=0.017）。孟德尔随机化分析证实了这一主要发现，表明血清肌酐与ALS风险降低相关（比值比：0.92，95%置信区间：0.86-0.98，P=0.01）。此外，基线血清肌酐水平较高与阿尔茨海默病发病风险降低相关（β=-4.89E-03，标准误=2.24E-03，P=0.03），尽管效应量较小。
这些发现增进了我们对肌酐在NDDs风险中作用的理解，提示了将肌酐作为ALS生物标志物的潜力，并对临床试验中治疗干预措施的设计具有启示意义。
