Myostatin and Insulin-Like Growth Factor 1 Are Biomarkers of Muscle Strength, Muscle Mass, and Mortality in Patients on Hemodialysis
Résumé
OBJECTIVE: Muscle strength is frequently altered in hemodialysis patients. In the present work, five potential muscle biomarkers have been studied in their ability to assess muscular strength, muscular mass and to predict mortality of hemodialysis patients: activin-A, procollagen III N-terminal peptide, follistatin, myostatin and insulin-like growth factor-1 (IGF-1). DESIGN AND METHODS: Three independent cohorts of prevalent hemodialysis patients (2 from Liège, Belgium and 1 from Marseille, France) were considered in this observational prospective study. The biomarkers were first measured in the Liege1 cohort. Two of them, myostatin and IGF-1, were then assessed in the whole population of patients (Liege1, Liege2 and Marseille). Muscle strength was assessed with handgrip strength (HGS) and muscle mass with bioimpedance analysis. One-year mortality predictive value of biomarkers was also studied in the Liège1 and Marseille cohorts. RESULTS: In the Liège1 cohort (n=67), HGS was only associated with concentrations of myostatin and IGF-1. These associations were confirmed in the whole population of 204 patients (r=0.37, P<0.001 and r=0.46, P<0.001, respectively) and remained significant (P<0.05) in multivariable models. The association between muscle mass and concentrations of myostatin and IGF-1were also significant. The ability of myostatin, IGF-1 and serum creatinine to detect a low HGS compared by Receiver Operating Characteristic curves analysis were not significantly different. Both myostatin and IGF-1 had a significant and comparable area under the curve to predict one-year mortality: 0.73 (95% CI: 0.64 to 0.83) and 0.72 (95% CI: 0.61 to 0.82), respectively. CONCLUSION: Our results suggest that myostatin and IGF-1 are two biomarkers of interest to assess muscle status of dialysis patients. Both biomarkers are associated with HGS, muscular mass, and one-year mortality.