Uric acid levels predict survival in men with amyotrophic lateral sclerosis

Abstract

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.

Crowdsourced analysis of clinical trial data to predict amyotrophic lateral sclerosis progression

“…4a). The list includes several features previously reported to predict ALS progression, including time from onset, age, forced vital capacity (FVC), site of onset, gender, weight [17][18][19][20] , as well as uric acid concentration in blood, a feature that has only been suggested recently as a predictor 20 . In addition, the challenge was successful in identifying nonstandard predictive features, opening the door to new insights into ALS disease mechanisms.…”

Urate as a Marker of Risk and Progression of Neurodegenerative Disease

“…Progression Inverse association [22][23][24] Inverse association [25][26][27][28] No association [29,30] Inverse association in HD, MSA, MCI [31][32][33] Laboratory…”

“…Higher urate levels are associated with slower clinical progression in Huntington's disease, multiple system atrophy, and mild cognitive impairment [29][30][31]. In ALS, most [25][26][27][28] but not all [32,33] studies found urate to represent a prognostic factor for survival. The reasons for these conflicting results in ALS are not completely clear and may be related to methodological differences, variable sample size, and a modest effect size.…”

Clinical Trial Designs in Amyotrophic Lateral Sclerosis: Does One Design Fit All?

“…Neurofilament light chain in cerebrospinal fluid (CSF) appears to increase as ALS progresses [19,[27][28][29][30][31]. Urate, which is lower in people with ALS than in controls, could serve a predictive or prognostic role [32][33][34][35][36]. Regulatory T cells, which are reduced in patients with rapidly progressive ALS, may be a predictive marker [37,38].…”