Uric acid levels predict survival in men with amyotrophic lateral sclerosis

Sabrina Paganoni, May Zhang, Alejandro Quiroz Zárate, Matthew Jaffa, Hong Yu, Merit E. Cudkowicz, Anne-Marie Wills

Elevated uric acid levels have recently been found to be associated with slower disease progression in Parkinson's disease, Huntington's disease, multiple system atrophy, and mild cognitive impairment. The aim of this study is to determine whether serum uric acid levels predict survival in amyotrophic lateral sclerosis (ALS). A total of 251 people with ALS enrolled in two multicenter clinical trials were included in our analysis. The main outcome measure was survival time, which was calculated as time to death, tracheostomy, or permanent assistive ventilation, with any event considered a survival endpoint. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching a survival endpoint according to baseline uric acid levels after adjusting for markers of disease severity (FVC, total ALSFRS-R score, time since symptom onset, diagnostic delay, BMI, bulbar vs. spinal onset, age, and riluzole use). There was a dose-dependent survival advantage in men, but not women, with higher baseline uric acid levels (logrank test: p = 0.018 for men, p = 0.81 for women). There was a 39% reduction in risk of death during the study for men with each 1 mg/dl increase in uric acid levels (adjusted HR: 0.61, 95% CI 0.39-0.96, p = 0.03). This is the first study to demonstrate that serum uric acid is associated with prolonged survival in ALS, after adjusting for markers of disease severity. Similar to previous reports in Parkinson's disease, this association was seen in male subjects only.