Uric acid levels predict survival in men with amyotrophic lateral sclerosis
- 540 Downloads
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.
KeywordsUric acid Urate Amyotrophic lateral sclerosis Predictor Survival
We would like to thank Patrick Sluss, Ph.D., and the Clinical Laboratory Research Core at Massachusetts General Hospital for performing the biochemical analyses and for their excellent technical support. We thank David Schoenfeld, Ph.D. and Alberto Ascherio, M.D., Dr. P.H. for helpful discussions about data analysis and interpretation. We thank Swati Aggarwal, M.D. for helping with study design. We would also like to thank the Massachusetts General Hospital Neurology Clinical Trials Unit and the members of the Northeast ALS Consortium (NEALS) for allowing access to the blood samples and clinical data that were used in this study. Finally, we thank patients and their families for participating in these clinical trials and for contributing to clinical research. Drs. Wills and Paganoni had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The study was supported by the Muscular Dystrophy Association and the Digiovanni ALS research fund.
Conflicts of interest
The authors declare that they have no conflicts of interest.
- 5.Ascherio A, LeWitt PA, Xu K, Eberly S, Watts A, Matson WR, Marras C, Kieburtz K, Rudolph A, Bogdanov MB, Schwid SR, Tennis M, Tanner CM, Beal MF, Lang AE, Oakes D, Fahn S, Shoulson I, Schwarzschild MA, Parkinson Study Group DATATOP Investigators (2009) Urate as a predictor of the rate of clinical decline in Parkinson disease. Arch Neurol 66:1460–1468PubMedCrossRefGoogle Scholar
- 6.Schwarzschild MA, Schwid SR, Marek K, Watts A, Lang AE, Oakes D, Shoulson I, Ascherio A, Parkinson Study Group PRECEPT Investigators, Hyson C, Gorbold E, Rudolph A, Kieburtz K, Fahn S, Gauger L, Goetz C, Seibyl J, Forrest M, Ondrasik J (2008) Serum urate as a predictor of clinical and radiographic progression in Parkinson disease. Arch Neurol 65:716–723PubMedCrossRefGoogle Scholar
- 18.Cudkowicz ME, Shefner JM, Simpson E, Grasso D, Yu H, Zhang H, Shui A, Schoenfeld D, Brown RH, Wieland S, Barber JR, Northeast ALS Consortium (2008) Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis. Muscle Nerve 38:837–844PubMedCrossRefGoogle Scholar
- 21.Zoccolella S, Beghi E, Palagano G, Fraddosio A, Samarelli V, Lamberti P, Lepore V, Serlenga L, Logroscino G (2006) SLAP registry (2006) Predictors of delay in the diagnosis and clinical trial entry of amyotrophic lateral sclerosis patients: a population-based study. J Neurol Sci 250:45–49PubMedCrossRefGoogle Scholar