Abstract：
BACKGROUND: Chronic kidney disease is linked to a disturbed fibroblast growth factor-23 (FGF23)-Klotho axis and an imbalance between myostatin and insulin-like growth factor-1 (IGF-1) expression. This cross-sectional study investigates the association of the FGF23-Klotho axis and myokine profile with serum interleukin-6 (IL-6) and their interactions in pediatric patients.
METHODS: Serum calcium, phosphorus, 25-hydroxyvitamin D, parathormone, c-terminal FGF23, a-Klotho, myostatin, follistatin, IGF-1, and IL-6 were measured in 53 patients with GFR < 60 ml/min/1,73m2. Myostatin to lean mass (LM) and to IGF-1 ratios were calculated. IL-6 level > 3rd quartile was considered as high.
RESULTS: Myostatin, IGF-1, and follistatin were correlated to LM (rs = 0.513, p < 0.001, rs = 0.652, p < 0.001, rs=-0.483, p < 0.001). Myostatin and follistatin were correlated to IGF-1 (rs = 0.340, p = 0.014, rs=-0.385, p = 0.005). Myostatin/LM but not myostatin or myostatin/IGF-1 ratio was significantly higher in CKD 5D patients (p = 0.001,p = 0.844, p = 0.111). Among mineral bone parameters, lnFGF23 was correlated to lnIL-6 (rs = 0.397, p = 0.004) and associated with high IL-6 (OR 1.905, 95% CI 1.023-3.548). Among myokines, myostatin/IGF-1 ratio was correlated to lnIL-6 (rs = 0.395, p = 0.004) and associated with high IL-6 (OR 1.113, 95% CI 1.028-1.205). All associations were adjusted to CKD stage. Myostatin was correlated to lnFGF23 (rs = 0.331, p = 0.025) and myostatin/IGF-1 ratio to lnKlotho (rs=-0.363, p = 0.013), after adjustment for CKD stage, lnIL-6 and other mineral bone parameters.
CONCLUSIONS: In pediatric CKD, FGF23 and myostatin/IGF-1 ratio are associated with IL-6, indicating a link between systemic inflammation, mineral bone, and myokine disorders. The correlations between myostatin and FGF23 and between myostatin/IGF-1 and Klotho suggest an interaction between mineral bone and muscle metabolism.
METHODS: Serum calcium, phosphorus, 25-hydroxyvitamin D, parathormone, c-terminal FGF23, a-Klotho, myostatin, follistatin, IGF-1, and IL-6 were measured in 53 patients with GFR < 60 ml/min/1,73m2. Myostatin to lean mass (LM) and to IGF-1 ratios were calculated. IL-6 level > 3rd quartile was considered as high.
RESULTS: Myostatin, IGF-1, and follistatin were correlated to LM (rs = 0.513, p < 0.001, rs = 0.652, p < 0.001, rs=-0.483, p < 0.001). Myostatin and follistatin were correlated to IGF-1 (rs = 0.340, p = 0.014, rs=-0.385, p = 0.005). Myostatin/LM but not myostatin or myostatin/IGF-1 ratio was significantly higher in CKD 5D patients (p = 0.001,p = 0.844, p = 0.111). Among mineral bone parameters, lnFGF23 was correlated to lnIL-6 (rs = 0.397, p = 0.004) and associated with high IL-6 (OR 1.905, 95% CI 1.023-3.548). Among myokines, myostatin/IGF-1 ratio was correlated to lnIL-6 (rs = 0.395, p = 0.004) and associated with high IL-6 (OR 1.113, 95% CI 1.028-1.205). All associations were adjusted to CKD stage. Myostatin was correlated to lnFGF23 (rs = 0.331, p = 0.025) and myostatin/IGF-1 ratio to lnKlotho (rs=-0.363, p = 0.013), after adjustment for CKD stage, lnIL-6 and other mineral bone parameters.
CONCLUSIONS: In pediatric CKD, FGF23 and myostatin/IGF-1 ratio are associated with IL-6, indicating a link between systemic inflammation, mineral bone, and myokine disorders. The correlations between myostatin and FGF23 and between myostatin/IGF-1 and Klotho suggest an interaction between mineral bone and muscle metabolism.
摘要：
背景：慢性肾脏疾病与成纤维细胞生长因子-23（FGF23）-Klotho轴紊乱以及肌肉生长抑制素和胰岛素样生长因子-1（IGF-1）表达失衡有关。这项横断面研究调查了FGF23-Klotho轴和肌动蛋白谱与血清白细胞介素-6（IL-6）及其在儿科患者中的相互作用的关联。
方法：血清钙，磷，25-羟基维生素D,甲状旁腺激素，c端FGF23，a-Klotho，肌肉生长抑制素,卵泡抑素,在53例GFR<60ml/min/1,73m2的患者中测量IGF-1和IL-6。计算肌肉生长抑制素与瘦体重(LM)和与IGF-1的比率。IL-6水平>第3四分位数被认为是高的。
结果：肌肉生长抑制素，IGF-1和卵泡抑素与LM相关(rs=0.513,p<0.001,rs=0.652,p<0.001,rs=-0.483,p<0.001)。肌肉生长抑制素和卵泡抑素与IGF-1相关（rs=0.340，p=0.014，rs=-0.385，p=0.005）。在CKD5D患者中，肌肉生长抑制素/LM而不是肌肉生长抑制素或肌肉生长抑制素/IGF-1比率显着升高（p=0.001，p=0.844，p=0.111）。在矿物骨参数中，lnFGF23与lnIL-6相关（rs=0.397，p=0.004），并与高IL-6相关（OR1.905，95％CI1.023-3.548）。在Myokines中,肌肉生长抑制素/IGF-1比值与lnIL-6相关(rs=0.395,p=0.004),与高IL-6相关(OR1.113,95%CI1.028-1.205)。所有关联均调整为CKD阶段。肌肉生长抑制素与lnFGF23相关（rs=0.331，p=0.025），肌肉生长抑制素/IGF-1与lnKlotho的比值相关（rs=-0.363，p=0.013），调整CKD阶段后，lnIL-6和其他矿物骨参数。
结论：在小儿CKD中，FGF23和肌肉生长抑制素/IGF-1比例与IL-6相关，表明全身性炎症之间存在联系，矿物骨,和肌动蛋白紊乱。肌肉生长抑制素和FGF23之间的相关性以及肌肉生长抑制素/IGF-1和Klotho之间的相关性表明矿物骨和肌肉代谢之间的相互作用。
方法：血清钙，磷，25-羟基维生素D,甲状旁腺激素，c端FGF23，a-Klotho，肌肉生长抑制素,卵泡抑素,在53例GFR<60ml/min/1,73m2的患者中测量IGF-1和IL-6。计算肌肉生长抑制素与瘦体重(LM)和与IGF-1的比率。IL-6水平>第3四分位数被认为是高的。
结果：肌肉生长抑制素，IGF-1和卵泡抑素与LM相关(rs=0.513,p<0.001,rs=0.652,p<0.001,rs=-0.483,p<0.001)。肌肉生长抑制素和卵泡抑素与IGF-1相关（rs=0.340，p=0.014，rs=-0.385，p=0.005）。在CKD5D患者中，肌肉生长抑制素/LM而不是肌肉生长抑制素或肌肉生长抑制素/IGF-1比率显着升高（p=0.001，p=0.844，p=0.111）。在矿物骨参数中，lnFGF23与lnIL-6相关（rs=0.397，p=0.004），并与高IL-6相关（OR1.905，95％CI1.023-3.548）。在Myokines中,肌肉生长抑制素/IGF-1比值与lnIL-6相关(rs=0.395,p=0.004),与高IL-6相关(OR1.113,95%CI1.028-1.205)。所有关联均调整为CKD阶段。肌肉生长抑制素与lnFGF23相关（rs=0.331，p=0.025），肌肉生长抑制素/IGF-1与lnKlotho的比值相关（rs=-0.363，p=0.013），调整CKD阶段后，lnIL-6和其他矿物骨参数。
结论：在小儿CKD中，FGF23和肌肉生长抑制素/IGF-1比例与IL-6相关，表明全身性炎症之间存在联系，矿物骨,和肌动蛋白紊乱。肌肉生长抑制素和FGF23之间的相关性以及肌肉生长抑制素/IGF-1和Klotho之间的相关性表明矿物骨和肌肉代谢之间的相互作用。
