Hydration measured by doubly labeled water in ALS and its effects on survival

Abstract

We present a study of hydration in ALS patients and its effects on survival. This was a multicenter study over 48 weeks in 80 ALS patients who underwent 250 individual measurements using doubly labeled water (DLW). Total body water (TBW) and water turnover (a surrogate for water intake) were 3.4% and 8.6% lower, respectively, in patients compared to age- and gender-matched healthy controls, and both significantly decreased over study duration. In 20% of patients, water turnover measured over 10 d was 2 standard deviations below the mean value in healthy controls. In a separate clinic cohort of 208 patients, water intake estimated from a de novo equation created from common clinical endpoints was a prognostic indicator of survival. Regardless of nutritional state assessed by BMI, survival was two-fold longer in the group above the median for estimated water intake, suggesting that hydration may be a more important predictor of survival than malnutrition. Risk factors for poor hydration were identified. Water intake equations recommended by US Centers for Medicare and Medicaid Services in healthy elderly were inaccurate for use in ALS patients. We developed equations to estimate TBW and water intake in ALS patients for use in clinics to accurately estimate hydration and improve clinical care.

Keywords:

• ALS
• doubly labeled water
• hydration
• water intake
• water turnover
• total body water
• survival

Acknowledgments

This study was supported by the National Institute of Neurological Disorders and Stroke grant RO1 NS045087; the General Clinical Research Centers grants at Columbia University (RR00645), University of Kentucky (RR02602), Penn State University (RR10732 and CO6-RR016499), University of Utah (RR00064) and the University of Vermont (RR00109); the National ALS Association; the ALS Hope Foundation; the Cynthia Shaw Crispen Endowment; the Kevin Heidrich/Team 7 Endowment; and the Department of Neurological Sciences ALS Research Fund, University of Vermont. The authors gratefully acknowledge the enthusiastic participation of ALS patients and caregivers, and Clinical Research Center staff at the participating institutions in undertaking this study. The authors thank Robin Conwit and Janice Cordell of the National Institute of Neurological Disorders and Stroke, and the members of the Data Safety Monitoring Board for their assistance in the course of this study.

Declaration of interest

MBB is a medical consultant for Accordant Health Services and on the speaker’s bureau for Grifols and Genzyme; EJK is a consultant for Neuraltus Pharmaceuticals, Inc. and CDC/ATSDR for the ALS Registry, DSMB member for Cytokinetics, Inc. and has research funding from Neuraltus Pharmaceuticals, Inc., Amylyx Pharmaceuticals, Inc. and Mallinckrodt Pharmaceuticals; HMM is on the Advisory Board of Cytokinetics, Inc., Mitsubishi-Tanabe Pharma and Sunovion Pharmaceuticals and has research funding from the Centers for Disease Control, Cytokinetics, Inc., Muscular Dystrophy Association, Tsumura & Co., Wings Over Wall Street Fund and Spastic Paraplegia Foundation; ZS is the Editor-in-Chief of Muscle & Nerve, a medical consultant for Cytokinetics, Inc. and Neuralstem, Inc. and has research funding from Biogen, Inc., Cytokinetics, Inc. and GlaxoSmithKline; RT is a medical advisory board member of the Myasthenia Gravis Foundation of America, a member of the Medical Education Council at Option Care and has research funding from Alexion Pharmaceuticals, Inc., Cytokinetics, Inc., Grifols, Inc., National ALS Association, UCB Pharma and Geisel School of Medicine at Dartmouth. CNS, DBH and DEM have no conflict of interest. The authors alone are responsible for the content and writing of this paper.

Supplementary material available online