血清肌酐与胱抑素C比值作为中国成人脊髓性肌萎缩症监测生物标志物的前瞻性队列研究。

Serum creatinine to cystatin C ratio as monitoring biomarker in Chinese adult spinal muscular atrophy: a prospective cohort study.

作者信息

Chen Sihui, Wang Qiong, Fu Jiajia, Wei Qianqian, Ou Ruwei, Lai Xiaohui, Chen Xueping, Shang Huifang

机构信息

Department of Neurology, West China Hospital of Sichuan University, No. 37 Guoxue Road, Chengdu, 610041, Sichuan, China.

Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

出版信息

Orphanet J Rare Dis. 2025 May 2;20(1):209. doi: 10.1186/s13023-025-03730-3.

DOI:10.1186/s13023-025-03730-3

PMID:40317045

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12046850/

Abstract

BACKGROUND

The creatinine to cystatin C ratio (CCR) can be used as a biomarker of muscle mass and strength, but no studies have evaluated whether it can be used as a biomarker to monitor the efficacy of treatment with nusinersen in Chinese adults with 5q-associated spinal muscular atrophy (SMA).

METHODS

In this prospective observational study, 28 adult SMA patients were followed for 18 months. Data on motor function and daily activities were collected using the Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), 6-Minute Walking Test (6WMT), and Barthel Index (BI). Serum levels of creatinine (Cr), creatine kinase (CK), and CCR were measured. Spearman correlation and linear mixed models analyzed the relationships between functional scores and laboratory indicators.

RESULTS

HFMSE scores showed significant improvement at Visit 5 (V5) [+ 1.04 points, p = 0.016), V6 (+ 1.61, p = 0.012), V7 (+ 1.93, p < 0.001), and V8 (+ 1.89, p < 0.001)], while RULM scores improved significantly at V5 (+ 2.00 points, p = 0.024), V7 (+ 2.00, p = 0.032), and V8 (+ 2.00, p < 0.001). The BI also exhibited significant improvement at V7 (+ 5.00, p < 0.001) and V8 (+ 2.50, p < 0.001). The 6MWT did not show significant improvement (p > 0.05). Serum CCR levels were significantly higher than baseline at V5 (+ 4.35 points, p < 0.001), V7 (+ 5.12, p < 0.001), and V8 (+ 6.59, p < 0.001). Cr levels were significantly higher than baseline at V5 (+ 2.39 points, p < 0.001) and V7 (+ 0.90, p < 0.001), while log10 CK levels remained unchanged (p > 0.05). Spearman correlation analysis revealed CCR showed the strongest correlation with functional scores, followed by Cr and log10 CK. Further linear mixed-effect model indicated that after adjusting for covariates, only CCR showed a dynamic positive correlation with HFMSE scores (β = 0.280; 95% CI 0.023-0.537, p = 0.033), while other serum indicators had no correlation with functional scores.

CONCLUSION

Long-term use of nusinersen effectively improves motor function and quality of life in adult SMA patients, and CCR may be a better indicator to reflect changes in motor function during treatment compared to other blood biomarkers.

摘要

背景

肌酐与胱抑素C比值（CCR）可作为肌肉质量和力量的生物标志物，但尚无研究评估其是否可作为监测中国5q相关脊髓性肌萎缩症（SMA）成人患者使用诺西那生治疗疗效的生物标志物。

方法

在这项前瞻性观察研究中，对28例成年SMA患者进行了18个月的随访。使用汉默史密斯功能运动量表扩展版（HFMSE）、修订上肢模块（RULM）、6分钟步行试验（6WMT）和巴氏指数（BI）收集运动功能和日常活动数据。测量血清肌酐（Cr）、肌酸激酶（CK）水平和CCR。采用Spearman相关性分析和线性混合模型分析功能评分与实验室指标之间的关系。

结果

HFMSE评分在第5次随访（V5）时显著改善[增加1.04分，p = 0.016]、V6（增加1.61分，p = 0.012）、V7（增加1.93分，p < 0.001）和V8（增加1.89分，p < 0.001），而RULM评分在V5时显著改善（增加2.00分，p = 0.024）、V7（增加2.00分，p = 0.032）和V8（增加2.00分，p < 0.001）。BI在V7时也显著改善（增加5.00分，p < 0.001）和V8（增加2.50分，p < 0.001）。6MWT未显示出显著改善（p > 0.05）。血清CCR水平在V5时显著高于基线（增加4.35分，p < 0.001）、V7（增加5.12分，p < 0.001）和V8（增加6.59分，p < 0.001）。Cr水平在V5时显著高于基线（增加2.39分，p < 0.001）和V7（增加0.90分，p < 0.001），而log10 CK水平保持不变（p > 0.05）。Spearman相关性分析显示CCR与功能评分的相关性最强，其次是Cr和log10 CK。进一步的线性混合效应模型表明，在调整协变量后，只有CCR与HFMSE评分呈动态正相关（β = 0.280；95%CI 0.023 - 0.537，p = 0.033），而其他血清指标与功能评分无相关性。