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Background <p>Reliable and accessible biomarkers for amyotrophic lateral sclerosis (ALS) are scarce. Creatinine (Cre) reflects muscle mass, whereas cystatin C (CysC) may reflect neurodegeneration without being directly influenced by muscle mass; however, both have limitations. We aimed to investigate whether the creatinine-to-cystatin C ratio (Cre/CysC) was cross-sectionally associated with functional status in patients with ALS.</p> Methods <p>We retrospectively analyzed 30 patients diagnosed with ALS at the National Organization Hospital Okinawa Hospital between 2021 and 2024. Baseline ALS Functional Rating Scale–Revised (ALSFRS-R) scores and serum Cre and CysC levels were recorded. Associations with the ALSFRS-R were assessed using Spearman’s correlation, with subgroup analyses by sex, site of onset, age at diagnosis, body mass index (BMI), and diagnostic delay. Multivariable analyses were performed to examine the independent association between Cre/CysC and ALSFRS-R while accounting for relevant clinical covariates.</p> Results <p>Cre/CysC showed a stronger cross-sectional correlation with ALSFRS-R (<i>r</i><sub>s</sub>=0.648, <i>p</i> = 0.0001) than Cre alone (<i>r</i><sub>s</sub> =0.427) or CysC (<i>r</i><sub>s</sub> =–0.119). Exploratory subgroup analyses showed generally positive associations in several subgroups, although no statistically significant association was observed in the small bulbar-onset subgroup. In multivariable analysis adjusted for age at onset and diagnostic delay, Cre/CysC remained independently associated with ALSFRS-R (β = 20.1, 95% CI 6.41–33.9, <i>p</i> = 0.006). Given the small sample size and cross-sectional design, these findings should be interpreted as exploratory.</p> Conclusions <p>Cre/CysC showed a stronger cross-sectional association with functional status than either marker alone. Because it is derived from routine laboratory tests, Cre/CysC may represent a simple exploratory measure associated with functional status in ALS. However, the present findings do not establish prognostic utility or fully account for disease stage and biological heterogeneity. Prospective longitudinal studies incorporating disease progression measures and broader clinical and genetic characterization are warranted.</p>

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Association between creatinine-to-cystatin C ratio and ALSFRS-R across clinical phenotypes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月25日

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  • Yoshihisa Fujiwara,
  • Akihiro Hashiguchi,
  • Shiori Yamashiro,
  • Hiroshi Seno,
  • Yuichiro Ohya,
  • Daigo Yasutomi,
  • Natsumi Fujisaki,
  • Miwako Kido,
  • Shugo Suwazono,
  • Takashi Tokashiki

摘要

Background

Reliable and accessible biomarkers for amyotrophic lateral sclerosis (ALS) are scarce. Creatinine (Cre) reflects muscle mass, whereas cystatin C (CysC) may reflect neurodegeneration without being directly influenced by muscle mass; however, both have limitations. We aimed to investigate whether the creatinine-to-cystatin C ratio (Cre/CysC) was cross-sectionally associated with functional status in patients with ALS.

Methods

We retrospectively analyzed 30 patients diagnosed with ALS at the National Organization Hospital Okinawa Hospital between 2021 and 2024. Baseline ALS Functional Rating Scale–Revised (ALSFRS-R) scores and serum Cre and CysC levels were recorded. Associations with the ALSFRS-R were assessed using Spearman’s correlation, with subgroup analyses by sex, site of onset, age at diagnosis, body mass index (BMI), and diagnostic delay. Multivariable analyses were performed to examine the independent association between Cre/CysC and ALSFRS-R while accounting for relevant clinical covariates.

Results

Cre/CysC showed a stronger cross-sectional correlation with ALSFRS-R (rs=0.648, p = 0.0001) than Cre alone (rs =0.427) or CysC (rs =–0.119). Exploratory subgroup analyses showed generally positive associations in several subgroups, although no statistically significant association was observed in the small bulbar-onset subgroup. In multivariable analysis adjusted for age at onset and diagnostic delay, Cre/CysC remained independently associated with ALSFRS-R (β = 20.1, 95% CI 6.41–33.9, p = 0.006). Given the small sample size and cross-sectional design, these findings should be interpreted as exploratory.

Conclusions

Cre/CysC showed a stronger cross-sectional association with functional status than either marker alone. Because it is derived from routine laboratory tests, Cre/CysC may represent a simple exploratory measure associated with functional status in ALS. However, the present findings do not establish prognostic utility or fully account for disease stage and biological heterogeneity. Prospective longitudinal studies incorporating disease progression measures and broader clinical and genetic characterization are warranted.