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Journal of Neurology

, Volume 259, Issue 9, pp 1923–1928 | Cite as

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 WillsEmail author
Original Communication

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.

Keywords

Uric acid Urate Amyotrophic lateral sclerosis Predictor Survival 

Notes

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.

Supplementary material

415_2012_6440_MOESM1_ESM.doc (66 kb)
Supplementary material 1 (DOC 66.5 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Sabrina Paganoni
    • 1
  • May Zhang
    • 1
  • Alejandro Quiroz Zárate
    • 2
  • Matthew Jaffa
    • 1
  • Hong Yu
    • 1
  • Merit E. Cudkowicz
    • 1
  • Anne-Marie Wills
    • 1
    Email author
  1. 1.Neurology Clinical Trials UnitMassachusetts General Hospital, Harvard Medical SchoolCharlestownUSA
  2. 2.Department of BiostatisticsHarvard School of Public HealthBostonUSA

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