Abstract
ObjectivesMyostatin (MSTN), a member of TGF-β superfamily, is produced in the skeletal muscle to inhibit myocyte differentiation. MSTN expression is increased in the skeletal muscle in patients with chronic kidney disease (CKD), which may play a role in the pathogenesis of sarcopenia or in the protein energy wasting (PEW). This observation implies that the plasma MSTN level may be correlated with kidney function. Thus, we conducted a cross-sectional study to evaluate the association between the plasma MSTN concentration and the estimated glomerular filtration rate (eGFR).Subjects and MethodsSubjects were 781 participants of a health examination performed in a rural area in Japan. Among them, 124 subjects were selected by stratified random sampling according to eGFR. Creatinine clearance (ClCr) by the Cockcroft-Gault equation was used as a measure of kidney function. Plasma concentration of MSTN was determined by ELISA.ResultsThe plasma MSTN level was not different between men (3.42±1.61 ng/mL) and women (3.27±1.43 ng/mL). In a simple regression analysis, the MSTN level was significantly correlated with eGFR (r = -0.25, p<0.01) and ClCr (r = -0.20, p<0.05) but not with age and BMI. In a multiple linear regression analysis, the MSTN level showed a negative correlation with eGFR (standardized β = -0.31, p<0.01) and ClCr (standardized β = -0.35, p<0.01) under the adjustment with age, sex, BMI and LDL-C. Weak correlation was observed between the MSTN level and BMI / the serum LDL-C level. When the subjects were stratified into 4 groups according to eGFR, MSTN was significantly greater in the groups with the lowest and the 2nd lowest eGFR (3.55±1.79 and 3.76±1.75 ng/mL, respectively) than the level in the group with the highest eGFR (2.77±0.85 ng/mL).ConclusionPlasma MSTN level was elevated in an early stage of CKD, which could be involved in the progression of sarcopenia.
Highlights
Nutritional status is a strong determinant of mortality, especially in patients with the chronic kidney disease (CKD)
When the subjects were stratified into 4 groups according to estimated glomerular filtration rate (eGFR), MSTN was significantly greater in the groups with the lowest and the 2nd lowest eGFR (3.55±1.79 and 3.76±1.75 ng/mL, respectively) than the level in the group with the highest eGFR (2.77±0.85 ng/mL)
Plasma MSTN level was elevated in an early stage of CKD, which could be involved in the progression of sarcopenia
Summary
Nutritional status is a strong determinant of mortality, especially in patients with the chronic kidney disease (CKD). PEW imposes significant influence on the patients’ prognosis, the pathogenesis of PEW remains to be elucidated [2]. Recent advance in this field indicated that myostatin (MSTN) expression was increased in the skeletal muscle in CKD patients at both mRNA and protein levels [3]. Administration of the anti-MSTN peptibody suppressed muscle wasting in a mouse model of CKD [5]. These findings suggested that MSTN played a pivotal role in the pathogenesis of PEW in CKD patients and can be a good therapeutic target [6]
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