Phosphatemia is an Independent Prognostic Factor in Amyotrophic Lateral Sclerosis.

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-04-26 DOI:10.1002/ana.27252

Rosario Vasta, Emanuele Koumantakis, Antonio Canosa, Umberto Manera, Maurizio Grassano, Francesca Palumbo, Sara Cabras, Enrico Matteoni, Francesca Di Pede, Filippo De Mattei, Filippo Vergnano, Jessica Mandrioli, Cecilia Simonini, Ilaria Martinelli, Fabiola De Marchi, Letizia Mazzini, Cristina Moglia, Andrea Calvo, Adriano Chiò

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引用次数: 0

Abstract

Objective: The objective of this study was to evaluate the prognostic value of several muscle damage biomarkers.

Methods: Data from Piemonte and Valle d'Aosta Amyotrophic Lateral Sclerosis (PARALS) were considered for this study. Survival was defined as the time from diagnosis to death, tracheostomy, or the censoring date. Blood levels of potassium, creatinine, creatine kinase, phosphorus, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) diagnosis were evaluated as potential prognostic biomarkers. A Cox model was developed for each biomarker and adjusted for sex, onset age, onset site, and diagnostic delay. Significant findings from PARALS were evaluated in the Pooled Resource Open-Access Amyotrophic Lateral Sclerosis Clinical Trials (PRO-ACT) database. Additionally, a joint model was constructed to evaluate the prognostic role of phosphatemia slope over time using longitudinal data from PRO-ACT.

Results: A total of 1,444 and 1,023 patients were included in the PARALS and PRO-ACT cohorts, respectively. Only creatinine (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.50-0.85) and phosphorus (HR = 1.14, 95% CI = 1.04-1.24) showed a significant association with survival in the PARALS cohort. These findings were further validated in the PRO-ACT cohort (creatinine HR = 0.21, 95% CI = 0.13-0.35, p < 0.0001; phosphorus HR = 2.35, 95% CI = 1.13-4.88, p = 0.02). Longitudinal data from the PRO-ACT database showed that an increase of 0.1 mmol/l per month in phosphate levels was also associated with a HR of 8.26 (95% CI = 1.07-96.6, p = 0.044).

Interpretation: Creatininemia was confirmed as a prognostic marker in amyotrophic lateral sclerosis (ALS). Additionally, both phosphatemia levels at diagnosis and its rate of change over time were identified as a potential prognostic marker for ALS. As with other blood biomarkers, phosphate levels are cost-effective and minimally invasive to measure, supporting their potential use in clinical trials. ANN NEUROL 2025.

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磷血症是肌萎缩性侧索硬化症的一个独立预后因素。

目的：本研究的目的是评估几种肌肉损伤生物标志物的预后价值。方法：本研究考虑了Piemonte和Valle d'Aosta肌萎缩性侧索硬化症（PARALS）的数据。生存期定义为从诊断到死亡、气管切开术或检查日期的时间。血液中钾、肌酐、肌酸激酶、磷、天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）作为潜在的预后生物标志物进行评估。针对每个生物标志物建立Cox模型，并根据性别、发病年龄、发病部位和诊断延迟进行调整。PARALS的重要发现在开放获取肌萎缩侧索硬化临床试验（PRO-ACT）数据库中进行了评估。此外，利用PRO-ACT的纵向数据，构建了一个联合模型来评估磷血症斜率随时间的预后作用。结果：PARALS组和PRO-ACT组分别纳入1444例和1023例患者。在PARALS队列中，只有肌酐（风险比[HR] = 0.65, 95%可信区间[CI] = 0.50-0.85）和磷（风险比[HR] = 1.14, 95% CI = 1.04-1.24）与生存率有显著相关性。这些发现在PRO-ACT队列中得到进一步验证（肌酐HR = 0.21, 95% CI = 0.13-0.35, p）。解释：肌酐血症被证实是肌萎缩侧索硬化症（ALS）的预后标志物。此外，诊断时的磷血症水平及其随时间的变化率被确定为ALS的潜在预后标志物。与其他血液生物标志物一样，磷酸盐水平具有成本效益和微创性，支持其在临床试验中的潜在应用。Ann neurol 2025。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.