基于FGF23/Klotho稳态观察口服糖皮质激素致生长障碍的临床研究

Clinical study on growth impairment induced by oral glucocorticoids based on FGF23/Klotho homeostasis observations

摘要:

目的 观察长期口服糖皮质激素（glucocorticosteroid, GC）抑制原发性肾病综合征（primary nephrotic syndrome, PNS）儿童生长与FGF23/Klotho比值变化的相关性。方法 前瞻性选取已停用GC 3个月以上，于2022年6—12月至河南中医药大学第一附属医院儿科医院复查的56例激素敏感型PNS儿童为研究对象。入院监测尿蛋白定性及定量后，尿蛋白复发者加用GC治疗，为GC组（n=29）；尿蛋白未复发者不加用GC治疗，为无GC组（n=27）。同期选取29例3岁至青春期前年龄的健康体检儿童作为对照组。比较各组身高、骨龄、增长速度及FGF23/Klotho比值等指标，并进行相关性分析。结果 GC组加用GC 1个月后的FGF23/Klotho比值高于无GC组（P<0.05），半年内的身高增长速度、骨龄增长速度均低于无GC组（P<0.05）。相关性分析显示PNS儿童治疗1个月后的FGF23/Klotho比值与治疗半年内的身高增长速度、骨龄增长速度均呈显著负相关（分别r=-0.356、-0.436，P<0.05）。结论 FGF23/Klotho稳态失衡是长期口服GC导致生长障碍的机制之一。

Abstract:

Objective To observe the correlation between growth impairment induced by long-term oral glucocorticoids (GC) therapy and the ratio of FGF23/Klotho in children with primary nephrotic syndrome (PNS).Methods A prospective study was conducted on 56 children with GC-sensitive PNS who had discontinued GC therapy for more than 3 months and revisited the Department of Pediatrics of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine between June 2022 and December 2022. After monitoring qualitative and quantitative urine protein levels upon admission, the children with proteinuria relapse were treated with GC (GC group; n=29), while those without relapse did not receive GC treatment (non-GC group; n=27). In addition, 29 healthy children aged 3 to prepuberty were selected as the control group. Height, bone age, growth rate, and the FGF23/Klotho ratio were compared among the groups. The correlations of the FGF23/Klotho ratio with height, bone age, and growth rate were analyzed.Results The FGF23/Klotho ratio in the GC group was significantly higher than that in the non-GC group after 1 month of GC therapy (P<0.05), and the height and bone age growth rates within 6 months were lower than those in the non-GC group (P<0.05). Correlation analysis showed significant negative correlations between the FGF23/Klotho ratio after 1 month of treatment and the growth rates of height and bone age within 6 months in children with PNS (r=-0.356 and -0.436, respectively; P<0.05).Conclusions The disturbance in FGF23/Klotho homeostasis is one of the mechanisms underlying the growth impairment caused by long-term oral GC therapy.