Effect of ferric citrate on serum phosphate and fibroblast growth factor 23 among patients with nondialysis-dependent chronic kidney disease: path analyses.
Effect of ferric citrate on serum phosphate and fibroblast growth factor 23 among patients with nondialysis-dependent chronic kidney disease: path analyses.
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DOI：
10.1093/ndt/gfy318
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发表时间：
2019-07-01
期刊：
影响因子：
--
通讯作者：
Chertow GM
中科院分区：
文献类型：
--
作者：
Block GA;Pergola PE;Fishbane S;Martins JG;LeWinter RD;Uhlig K;Neylan JF;Chertow GM
在非透析依赖性慢性肾病（NDD-CKD）和缺铁性贫血（IDA）患者中，柠檬酸铁增加血红蛋白和铁参数，降低血清磷酸盐和成纤维细胞生长因子23 (FGF23)，一种关键的磷酸盐调节激素。我们对一项3期试验进行了事后分析，以探索铁替代、血清磷酸盐变化和FGF23调节之间的关系。我们采用多变量回归和纵向混合效应模型分别确定和确认基线人口统计学和实验室变量是否与柠檬酸铁诱导的血清磷酸盐或FGF23浓度变化相关。我们采用通径分析来确定FGF23浓度的变化是否通过血清磷酸盐和/或转铁蛋白饱和度（TSAT）的变化介导。我们分别分析了117例和115例柠檬酸铁治疗和安慰剂治疗的患者。在16周时，与安慰剂相比，柠檬酸铁仅在基线血清磷酸盐升高（≥4.5 mg/dL）的患者中显著降低了血清磷酸盐（P = 0.006），而在基线血清磷酸盐在人群参考范围内的患者中没有降低血清磷酸盐。柠檬酸铁降低完整FGF23和c端FGF23部分是通过TSAT （c端FGF23）和血清磷酸盐（完整FGF23）的变化，部分是通过未知/未测量的机制。柠檬酸铁降低血清FGF23浓度（部分通过对血清磷酸盐和铁平衡的影响），并没有降低基线血清磷酸盐浓度在人群参考范围内的患者的血清磷酸盐。
Among patients with nondialysis-dependent chronic kidney disease (NDD-CKD) and iron-deficiency anemia (IDA), ferric citrate increases hemoglobin and iron parameters and reduces serum phosphate and fibroblast growth factor 23 (FGF23), a key phosphate-regulating hormone. We conducted post hoc analyses of a phase 3 trial to explore associations between iron replacement, serum phosphate changes and FGF23 regulation. We employed multivariable regression and longitudinal mixed-effects models to identify and confirm, respectively, whether baseline demographic and laboratory variables were associated with ferric citrate-induced changes in serum phosphate or FGF23 concentrations. We employed path analyses to determine whether changes in FGF23 concentrations were mediated via changes in serum phosphate and/or transferrin saturation (TSAT). We analyzed a total of 117 and 115 ferric citrate-treated and placebo-treated patients, respectively. At 16 weeks, ferric citrate significantly reduced serum phosphate versus placebo (P = 0.006) only among patients with elevated baseline serum phosphate (≥4.5 mg/dL) and did not reduce serum phosphate among patients with baseline serum phosphate within the population reference range. Ferric citrate reduced intact FGF23 and C-terminal FGF23 partially via changes in TSAT (for C-terminal FGF23) and serum phosphate (for intact FGF23) and partially via unknown/unmeasured mechanisms. Ferric citrate reduced serum FGF23 concentrations (partially via effects on serum phosphate and iron balance) and did not reduce serum phosphate among patients with baseline serum phosphate concentrations within the population reference range.
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