Background and objectives Plasma fibroblast growth factor 23 (FGF23) concentrations increase early in the course of CKD in children. High FGF23 levels associate with progression of CKD in adults. Whether FGF23 predicts CKD progression in children is unknown.
Design, setting, participants, & measurements We tested the hypothesis that high plasma FGF23 is an independent risk factor for CKD progression in 419 children, aged 1–16 years, enrolled in the Chronic Kidney Disease in Children (CKiD) cohort study. We measured plasma FGF23 concentrations at baseline and determined GFR annually using plasma disappearance of iohexol or the CKiD study estimating equation. We analyzed the association of baseline FGF23 with risk of progression to the composite end point, defined as start of dialysis or kidney transplantation or 50% decline from baseline GFR, adjusted for demographics, baseline GFR, proteinuria, other CKD-specific factors, and other mineral metabolites.
Results At enrollment, median age was 11 years [interquartile range (IQR), 8–15], GFR was 44 ml/min per 1.73 m2 (IQR, 33–57), and FGF23 was 132 RU/ml (IQR, 88–200). During a median follow-up of 5.5 years (IQR, 3.5–6.6), 32.5% of children reached the progression end point. Higher FGF23 concentrations were independently associated with higher risk of the composite outcome (fully adjusted hazard ratio, 2.52 in the highest versus lowest FGF23 tertile; 95% confidence interval, 1.44 to 4.39, P=0.002; fully adjusted hazard ratio, 1.33 per doubling of FGF23; 95% confidence interval, 1.13 to 1.56, P=0.001). The time to progression was 40% shorter for participants in the highest compared with the lowest FGF23 tertile. In contrast, serum phosphorus, vitamin D metabolites, and parathyroid hormone did not consistently associate with progression in adjusted analyses.
结果 纳入的中位年龄为11岁（25%-75%百分位 8-15），中位GFR是44ml/min每1.73m2（25%-75%百分位 33-57），FGF23中位数132RU/ml(25%-75%百分位88-200).中位随访5.5年（25%-75%百分位 3.5-6.6）之后，32.5%的儿童达到终点。FGF23水平升高与复合终点风险升高独立相关（调整后风险比 FGF23最高的1/4相对最低的1/4HR 2.52[95%CI 1.44,4.39],P=0.002;FGF23每升高一倍，HR 1.33[95%CI 1.13,1.56] P=0.001）FGF23最高的1/4与最低的1/4相比，进展所需的时间降低40%。而血清磷，维生素D代谢产物，甲状旁腺素调整后与CKD进展没有稳定的相关。
Conclusions High plasma FGF23 is an independent risk factor for CKD progression in children.