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Uric acid levels predict survival in men with amyotrophic lateral sclerosis

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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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown Navy Yard, Building 149,149 13th Street, 2nd Floor, Room 2274, Charlestown, MA, 02129, USA

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

  2. Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

    Alejandro Quiroz Zárate

Authors
  1. Sabrina Paganoni
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  2. May Zhang
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  3. Alejandro Quiroz Zárate
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  4. Matthew Jaffa
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  5. Hong Yu
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  6. Merit E. Cudkowicz
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  7. Anne-Marie Wills
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Corresponding author

Correspondence to Anne-Marie Wills.

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Paganoni, S., Zhang, M., Quiroz Zárate, A. et al. Uric acid levels predict survival in men with amyotrophic lateral sclerosis. J Neurol 259, 1923–1928 (2012). https://doi.org/10.1007/s00415-012-6440-7

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  • DOI: https://doi.org/10.1007/s00415-012-6440-7

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