TY - JOUR
T1 - Phosphatemia is an Independent Prognostic Factor in Amyotrophic Lateral Sclerosis
AU - Vasta, Rosario
AU - Koumantakis, Emanuele
AU - Canosa, Antonio
AU - Manera, Umberto
AU - Grassano, Maurizio
AU - Palumbo, Francesca
AU - Cabras, Sara
AU - Matteoni, Enrico
AU - Di Pede, Francesca
AU - De Mattei, Filippo
AU - Vergnano, Filippo
AU - Mandrioli, Jessica
AU - Simonini, Cecilia
AU - Martinelli, Ilaria
AU - De Marchi, Fabiola
AU - Mazzini, Letizia
AU - Moglia, Cristina
AU - Calvo, Andrea
AU - Chiò, Adriano
N1 - Publisher Copyright:
© 2025 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2025/8
Y1 - 2025/8
N2 - 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;98:286–293.
AB - 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;98:286–293.
UR - https://www.scopus.com/pages/publications/105003811859
U2 - 10.1002/ana.27252
DO - 10.1002/ana.27252
M3 - Article
SN - 0364-5134
VL - 98
SP - 286
EP - 293
JO - Annals of Neurology
JF - Annals of Neurology
IS - 2
ER -