Cystatin C is associated with poor survival in amyotrophic lateral sclerosis patients

Qirui Jiang; Yuan Guo; Tianmi Yang; Shirong Li; Yanbing Hou; Junyu Lin; Yi Xiao; Ruwei Ou; Qianqian Wei; Huifang Shang

doi:10.3389/fnins.2023.1309568

Cystatin C is associated with poor survival in amyotrophic lateral sclerosis patients

Front Neurosci. 2024 Jan 5:17:1309568. doi: 10.3389/fnins.2023.1309568. eCollection 2023.

Authors

Qirui Jiang^#¹, Yuan Guo^#², Tianmi Yang¹, Shirong Li^{1

3}, Yanbing Hou¹, Junyu Lin¹, Yi Xiao¹, Ruwei Ou¹, Qianqian Wei¹, Huifang Shang¹

Affiliations

¹ Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
² Outpatient Department, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
³ Department of Neurology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.

^# Contributed equally.

Abstract

Background: Cystatin C (CysC) levels in amyotrophic lateral sclerosis (ALS) have been found changes, however, the associations between serum CysC levels and the progression and survival of ALS remain largely unknown.

Methods: A total of 1,086 ALS patients and 1,026 sex-age matched healthy controls (HCs) were enrolled in this study. Serum CysC, other renal function, and metabolic parameters were measured. Correlation analysis and binary logistic regression were used to explore the factors related to serum CysC. Kaplan-Meier curve and Cox regression model were used for survival analysis.

Results: CysC levels were significantly higher in ALS patients compared to HCs (0.94 vs. 0.85 mg/L, p < 0.001). Compared with ALS patients with lower CysC levels, those with higher CysC levels had an older age of onset, significantly lower ALSFRS-R scores (40.1 vs. 41.3, p < 0.001), a faster disease progression rate (0.75 vs. 0.67, p = 0.011), and lower frontal lobe function scores (15.8 vs. 16.1, p = 0.020). In the correlation analysis, CysC levels were significantly negatively correlated with ALSFRS-R scores (r = -0.16, p < 0.001). Additionally, ALS patients with higher CysC levels had significantly shorter survival time (40.0 vs. 51.8, p < 0.001) compared to patients with lower CysC levels. Higher CysC levels were associated with a higher risk of death in Cox analysis (HR: 1.204, 95% CI: 1.012-1.433). However, when treatment was included in the model, the result was no longer significant.

Conclusion: CysC levels in ALS patients were higher compared to HCs. Higher CysC levels were associated with greater disease severity, faster progression rate and shorter survival, needing early intervention.

Keywords: amyotrophic lateral sclerosis; biomarker; clinical; cystatin C; prognosis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Sichuan Science and Technology Program (grant no. 2022ZDZX0023), the National Natural Science Foundation of China (grant no. 82101485), and Science and Technology commission foundation of Chengdu City (grant no. 2021-YF05-00242-SN).