成纤维细胞生长因子 23 和可溶性 klotho 在慢性肾脏病患儿中的变化。
Fibroblast growth factor 23 and soluble klotho in children with chronic kidney disease.
机构信息
Renal Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
出版信息
Nephrol Dial Transplant. 2013 Jan;28(1):153-61. doi: 10.1093/ndt/gfs411. Epub 2012 Nov 23.
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
背景
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。
方法
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。
结果
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。
结论
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。
Zotero 插件