Urine specific gravity to identify and predict hydration need in ALS

Abstract

Introduction: Multiple factors contribute to increased risk of dehydration in amyotrophic lateral sclerosis (ALS), which contributes to shortened survival independent of nutritional status. The assessment of hydration by doubly labeled water is restricted due to the limited availability of this gold standard technique for clinical use. This prompted us to examine the utility of urine-specific gravity (USG) as a predictor of hydration need in ALS subjects. Material and Methods: Using data from a multicenter study of 80 ALS subjects with 250 visits, we conducted a secondary analysis of the original data set from doubly labeled water experiments. We used a cross-section of the data (one visit per 75 subjects) in the model selection step (“test set”), and a repeated measures analysis in the validation step with data from 63 subjects and 142 follow-up visits. The sensitivity to detect inadequate water turnover rate (a surrogate for water intake) was the goal of the predictive model presented for clinical use. Results and discussion: The final predictive model to estimate water requirement included USG, gender, body mass index, and the ALSFRS gross motor subscale score. We developed a best-fit equation to estimate water intake from USG, determine hydration status, and improve clinical care of real-world ALS subjects.

Keywords:

• ALS
• doubly labeled water
• water intake
• water turnover
• urine specific gravity

Acknowledgments

The authors gratefully acknowledge the enthusiastic participation of ALS patients, caregivers, and Clinical Research Center staff at the participating institutions in 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. Finally, we thank Ms. Molly Partelow for the formatting, figure editing, and proofreading of the manuscript.

The ALS Nutrition/NIPPV Study Group members and participating institutions for the Nutrition sites are as follows: University of Kentucky Coordination Center (Edward J. Kasarskis, Richard J. Kryscio, Marta S. Mendiondo, Stephen Wells, Christie Shrestha, Margaret Healey, Megan Thompson, Lan Chi T. Luu, Carmen Saylor, Kathryn Vanderpool, Irina Kasarskis, Maria Malguizo, Renato Moreira, and Stephen Welch); Columbia University (Hiroshi Mitsumoto, Jackie Montes, Daniel Bell, Wahida Karmally, Megan Tubman, Kate Dalton, and Jonathan Hupf); Pennsylvania State University (Zachary Simmons, Helen Stephens, Ally Brothers, Susan Deiling, and Michelle Heckenluber); University of Utah (Mark B. Bromberg and Summer Davis); University of Vermont site for DLW studies (Rup Tandan, Chris Potter, Dwight Matthews, Shannon Lenox, and Jesse Gardner); Data and Safety Monitoring Board (Robert L. Sufit, Laurie Gutmann, Peng Huang, and Noah Lechtzin); NIH Program Management (Robin A. Conwit and Janice Cordell).

Declaration of interest

The authors report no conflicts of interest.

Additional information

Funding

This study was supported by the following: National Institute of Neurological Disorders and Stroke grant RO1 NS045087; General Clinical Research Center 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.