SP650MYOSTATIN: A NEW BIOMARKER OF MUSCLE STRENGTH IN HEMODIALYSIS PATIENTS

Abstract

INTRODUCTION AND AIMS: Muscle strength is associated with physical performance, quality of life and survival in hemodialysis patients. However, its measurement requires specific tools and is time consuming. Identification of easy-to-use biomarkers is crucial to identify patients with impaired muscle strength. Plasma concentration of creatinine is until now the best biomarker, but it is influenced by dialysis quality and renal residual function. Myostatin, a chalone protein of muscle physiology mainly produced by striated muscle cells, and IGF-1 (insulin growth factor 1), an anabolic muscle hormone are two potential candidates as muscle strength biomarker. METHODS: We conducted an observational prospective study in two hemodialysis facilities in Europe (Belgium and France). Hemodialysis patients' handgrip strength (HGS) was measured in standardized procedures. Normal HGS values were defined as recommended by the European Working Group on Sarcopenia in Older People:>20 kg for women and>30 kg for men. Plasma IGF-1 (IDS Isys) and myostatin (R&D) concentrations were measured in serum before hemodialysis session as well as creatinine. All medical parameters were recorded. Patients survival was followed-up during one year. In ten patients, myostatin concentration was measured before and after the hemodialysis session to assess if its concentration is modified by the procedure. RESULTS: The study included 133 hemodialysis (72 from Marseille, France and 61 from Liège, Belgium). Mean age was 70.5±17.0 years, 60.9% of patients were men and 41.4% had diabetes. Mean myostatin concentration was 258461777 pg/L and mean IGF-1 concentration was 131667 mg/L. HGS was normal in only 31% of patients and the 1-year mortality was 23.3%. Myostatin and IGF-1 were correlated with HGS (q=0.56 p<0.001 and q=0.45 p<0.001, respectively). Areas under ROC curves for predicting low HGS were 0.71, 0.73 and 0.78, for creatinine, IGF-1 and myostatin, respectively. The AUC was thus higher for myostatin than for creatinine although the difference was not significant. Areas under ROC curves for predicting death at one year were 0.65, 0.71 and 0.72 for creatinine, IGF-1 and myostatin, respectively. There again, the AUC was higher for myostatin than for creatinine but the difference was not significant. Mean intradialytic myostatin reduction ratio was-1.6±13.8% indicating that myostatin concentration is not much influenced by hemodialysis. CONCLUSIONS: IGF-1 and still more myostatin seem promising biomarkers of muscle strength. Myostatin is efficient to detect low muscle strength in hemodialysis patients, with the advantage of being not influenced by dialysis procedure. Interestingly, myostatin was also associated with one-year mortality. More studies are needed to confirm the everyday practice interest of myostatin as a muscle strength biomarker.