Serum Creatinine, a Biomarker for Muscle Mass in Amyotrophic Lateral Sclerosis (ALS), Predicts Loss of Ambulation Measured by ALS Functional Rating Scale-Revised Walking Item Score (ALSFRS-Rw) (P4.085)

OBJECTIVE: To define the relationship between serum creatinine and ALSFRS-Rw cross-sectionally and longitudinally over time in a clinic-based ALS patient population at Carolinas Healthcare System Neuromuscular/ALS-MDA Center BACKGROUND: Serum creatinine has been identified as a muscle mass biomarker related to the diagnosis and rate of progression of ALS and bulbar spinal muscular atrophy (Kennedy9s disease) in French, Japanese and American ALS patients (Paillisse,2005; Ikeda,2009; Ikeda, 2012; Hashizume,2012; Miller, 2012). Recent analysis of clinical staging in ALS patients has identified increased burden of leg involvement in El Escorial Criteria-Clinically Definite ALS patients (Brooks,2012). DESIGN/METHODS: Serum creatinine at first and subsequent clinic visits was compared with ALSFRS-R total score and ALSFRS-Rw from 2010-2012 in 311 ALS patients [183M;128F; 55.7±12.7(SD)years]. Cross-sectional analysis of all data as well as change in serum creatinine and ALSFRS-Rw between first and subsequent visits was analyzed with statistical software [MedCalc Software, Ostend, Belgium www.medcalc.org/]. RESULTS: Serum creatinine cross-sectionally decreased significantly with decreasing ALSFRS-Rw category [Equation - Creatinine=0.54(95%CI:0.49-0.58)+0.09(95%CI:0.07-0.11)•ALSFRS-Rw (R2=0.2082: P<0.001)]. Moreover, in individual ALS patients, change in serum creatinine decreased proportionate to decrease in ALSFRS-Rw [DeltaCreatinine=-0.11(95%CI:-0.16-0.05)+0.08(95%CI:0.04-0.12)•ALSFRS-Rw (R2=0.1506:P<0.001)]. CONCLUSIONS: Decrease in serum creatinine significantly predicted change in ambulation measured by ALSFRS-Rw longitudinally. Further analysis is required to determine whether leg function alone and leg muscle mass are the major determinants of serum creatinine in ALS patients over the course of the disease. Study Supported by: Carolinas ALS Research Fund/Pinstripes Fund/Carolinas Garden of Hope/Carolinas Healthcare Foundation Disclosure: Dr. Brooks has received personal compensation for activities with Biogen Idec, Avanir Pharmaceuticals, Acorda Therapeutics, Cytokinetics, Synapse, and the National Institute of Neurological Disorders and Stroke. Dr. Brooks has received research support from Biogen Idec, Avanir Pharmaceuticals, Cytokinetics, Neuraltus Pharmaceuticals, GlaxoSmithKline, Inc., and the National Institute of Neurological Disorders and Stroke. Dr. Fischer has nothing to disclose. Dr. Sanjak has nothing to disclose. Dr. Holsten has nothing to disclose. Dr. Kandinov has nothing to disclose. Dr. Bockenek has nothing to disclose. Dr. Bravver has received research support from Biogen Idec, Avanier, Cytokinetics Pharmaceuticals, Neuraltus Pharmaceuticals, GlaxoSmithKline Inc., the National Institute of Neurological Disorders and Stroke, and the Clinical Research Consortium. Dr. Desai has received personal compensation for activities with Purdue Pharma and UCB Pharma as a speaker. Dr. Story has nothing to disclose. Dr. Pacicco has nothing to disclose. Dr. Lindblom has nothing to disclose. Dr. Langford has nothing to disclose. Dr. Wright has nothing to disclose. Dr. Ward has nothing to disclose. Dr. Lucas has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Nichols has nothing to disclose. Dr. Lary has nothing to disclose. Dr. Nemeth has nothing to disclose. Dr. Russo has received personal compensation for activities with Teva Neuroscience and Biogen Idec as a consultant.