Longitudinal FGF23 and Klotho axis characterization in children treated with chronic peritoneal dialysis.
Longitudinal FGF23 and Klotho axis characterization in children treated with chronic peritoneal dialysis.
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DOI：
10.1093/ckj/sfu074
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发表时间：
2014-10
影响因子：
4.6
通讯作者：
Ugarte MF
中科院分区：
文献类型：
--
作者：
Cano FJ;Freundlich M;Ceballos ML;Rojo AP;Azocar MA;Delgado IO;Ibacache MJ;Delucchi MA;Lillo AM;Irarrázabal CE;Ugarte MF
成纤维细胞生长因子-23（FGF 23）和辅因子Klotho是慢性肾脏病（CKD）矿物质代谢的关键调节因子，但对其产生的调节机制知之甚少。本研究评估了慢性腹膜透析（PD）儿童FGF 23和Klotho水平的纵向变化及其调节因素。在1年的随访期间，测量了PD儿童的FGF 23、Klotho、25（OH）维生素D、1，25-二羟维生素D和甲状旁腺激素（PTH）血浆浓度。除了矿物质代谢变量外，还对人体测量和透析参数进行了评价。31例慢性PD患者随访12个月。与对照组相比，第1个月的FGF 23平均血浆水平显著增加，分别为215.1 ± 303.6和9.4 ± 5.7 pg/mL（P < 0.001）。与对照组相比，患者的基线Klotho水平低41%，分别为132.1 ± 58和320 ± 119.4 pg/mL（P < 0.001），并且与FGF 23和磷水平无关。在第12个月，FGF 23（195 ± 300 pg/mL）和Klotho水平（130 ± 34 pg/mL）保持与基线值相似。Log-FGF 23与身高/年龄Z评分（r=-0.38）和残余肾功能（r =-0.44）显著相关，但与血清磷、磷酸盐摄入量、PTH和维生素D水平无关。log-FGF 23与第1、6和12个月时的钙水平密切相关，然而，如果血清磷>6 mg/dL，则这种关系减弱。通过多元回归分析，钙是决定FGF 23水平的最强变量。在这项纵向研究中，与对照组相比，PD儿童的FGF 23水平显著升高，Klotho水平降低。FGF 23水平似乎主要受血清钙调节，在每次测量时显示出显著相关性。这种关系在磷>6 mg/dL的患者中消失。这些观察结果可能对CKD患者磷酸盐稳态的治疗管理产生重要影响。
Fibroblast Growth Factor-23 (FGF23) and cofactor Klotho are key regulators of mineral metabolism in chronic kidney disease (CKD), but little is known about the mechanisms that regulate their production. This study evaluates longitudinal changes of FGF23 and Klotho levels and their regulatory factors in children on chronic peritoneal dialysis (PD). FGF23, Klotho, 25(OH) vitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) plasma concentrations were measured during 1 year of follow-up in PD children. Anthropometric and dialytical parameters were evaluated in addition to mineral metabolism variables. Thirty-one patients under chronic PD were followed for 12 months. FGF23 mean plasma levels at Month 1 were significantly increased compared with controls, 215.1 ± 303.6 versus 9.4 ± 5.7 pg/mL, respectively (P < 0.001). Baseline Klotho levels were 41% lower in patients compared with controls, 132.1 ± 58 versus 320 ± 119.4 pg/mL, respectively (P < 0.001), and did not correlate with FGF23 and phosphorus levels. At Month 12, FGF23 (195 ± 300 pg/mL) and Klotho levels (130 ± 34 pg/mL) remained similar to baseline values. Log-FGF23 correlated significantly with height/age Z score (r= −0.38) and residual renal function (r = −0.44), but no correlation was found with serum phosphorus, phosphate intake, PTH and vitamin D levels. The log-FGF23 strongly correlated with calcium levels at Months 1, 6 and 12, however, this relationship was blunted if serum phosphorus was >6 mg/dL. By multiple regression analysis, calcium was the strongest variable determining FGF23 levels. In this longitudinal study, FGF23 levels are markedly increased, and Klotho levels are reduced in PD children compared with controls. FGF23 levels appeared to be regulated primarily by serum calcium, showing a significant correlation at each time of measurement. This relationship was lost in patients with phosphorus >6 mg/dL. These observations may have important consequences to the therapeutic management of phosphate homeostasis in CKD patients.