ArticleNeurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2025
Association of creatinine level with neurodegenerative disorders: a prospective cohort study and Mendelian randomization analysis.
Article in Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMultiple 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.
methodsUtilizing 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.
resultsA 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.
conclusionsThese 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.
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