Renal Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Nephrol Dial Transplant. 2013 Jan;28(1):153-61. doi: 10.1093/ndt/gfs411. Epub 2012 Nov 23.
Fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone, is elevated in chronic kidney disease (CKD). There are scarce data on the levels of its essential co-receptor klotho, and longitudinal changes in FGF23 levels are also unknown.
We examined FGF23 and soluble klotho (s-klotho) levels over 1 year in 154 children with CKD Stages 1-5 (CKD1-5), were on dialysis or who have received a transplantation.
In children with CKD1-5 and who were receiving dialysis, FGF23 correlated inversely with the estimated glomerular filtration rate (eGFR) (P < 0.001), whereas a decrease in s-klotho was observed with a lower eGFR (P = 0.01). There was no correlation between FGF23 and serum phosphate (P) or parathyroid hormone (PTH) in our cohort wherein 89 and 66%, respectively, had normal levels. FGF23 increased by 6-fold over a 12-month period in children with eGFR of 15-29 mL/min/1.73 m(2), with an overall 5% annual increase in the CKD1-5 and dialysis cohort. High FGF23 levels were seen with high calcium (Ca) levels (P < 0.001). FGF23 levels were high when 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were deficient (P = 0.05 and P < 0.001, respectively). s-klotho levels correlated positively with 25(OH)D (P < 0.001) and negatively with PTH (P = 0.04) and age (P = 0.03). Multivariate regression analysis demonstrated a strong relationship between FGF23 and eGFR, whereas the association between s-klotho and eGFR as observed in univariate analysis was lost following the adjustment of confounders. In transplanted patients, FGF23 correlated with eGFR (P = 0.02) and 25(OH)D (P = 0.05).
This study shows increasing FGF23 and reduced s-klotho levels with progressive renal failure even in a population of children with well-controlled P levels. Novel associations between FGF23 and serum Ca as well as 25(OH)D warrant further investigation.
成纤维细胞生长因子 23（FGF23）是一种骨源磷酸尿激素，在慢性肾脏病（CKD）中升高。关于其必需辅助受体 klotho 的水平的数据很少，并且 FGF23 水平的纵向变化也未知。
我们在 154 名患有 CKD 1-5 期（CKD1-5）、接受透析或接受移植的儿童中，在 1 年内检查了 FGF23 和可溶性 klotho（s-klotho）水平。
在患有 CKD1-5 期并接受透析的儿童中，FGF23 与估算肾小球滤过率（eGFR）呈负相关（P<0.001），而 s-klotho 则随着 eGFR 的降低而下降（P=0.01）。在我们的队列中，89%和 66%的患者血清磷酸盐（P）和甲状旁腺激素（PTH）水平正常，而 FGF23 与两者均无相关性。在 eGFR 为 15-29 mL/min/1.73 m²的儿童中，FGF23 在 12 个月内增加了 6 倍，CKD1-5 和透析队列的年增长率为 5%。高 FGF23 水平与高钙（Ca）水平有关（P<0.001）。当 25-羟维生素 D [25（OH）D]和 1,25-二羟维生素 D [1,25（OH）（2）D]缺乏时，FGF23 水平升高（P=0.05 和 P<0.001）。s-klotho 水平与 25（OH）D 呈正相关（P<0.001），与 PTH（P=0.04）和年龄（P=0.03）呈负相关。多元回归分析表明，FGF23 与 eGFR 之间存在很强的关系，而在单变量分析中观察到的 s-klotho 与 eGFR 之间的关系在调整混杂因素后消失。在移植患者中，FGF23 与 eGFR（P=0.02）和 25（OH）D（P=0.05）相关。
本研究表明，即使在 P 水平控制良好的儿童人群中，随着肾功能衰竭的进展，FGF23 增加和 s-klotho 水平降低。FGF23 与血清 Ca 以及 25（OH）D 之间的新关联值得进一步研究。
