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.
关键词
原发性肾病综合征 /
糖皮质激素 /
生长障碍 /
FGF23 /
Klotho /
儿童
Key words
Primary nephrotic syndrome /
Glucocorticosteroid /
Growth impairment /
FGF23 /
Klotho /
Child
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
1 Trautmann A, Boyer O, Hodson E, et al. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome[J]. Pediatr Nephrol, 2023, 38(3): 877-919. PMID: 36269406. PMCID: PMC9589698. DOI: 10.1007/s00467-022-05739-3.
2 Ma J, Siminoski K, Alos N, et al. Impact of vertebral fractures and glucocorticoid exposure on height deficits in children during treatment of leukemia[J]. J Clin Endocrinol Metab, 2019, 104(2): 213-222. PMID: 30247635. PMCID: PMC6291659. DOI: 10.1210/jc.2018-01083.
3 Delucchi á, Toro L, Alzamora R, et al. Glucocorticoids decrease longitudinal bone growth in pediatric kidney transplant recipients by stimulating the FGF23/FGFR3 signaling pathway[J]. J Bone Miner Res, 2019, 34(10): 1851-1861. PMID: 31099911. DOI: 10.1002/jbmr.3761.
4 Feger M, Ewendt F, Strotmann J, et al. Glucocorticoids dexamethasone and prednisolone suppress fibroblast growth factor 23 (FGF23)[J]. J Mol Med (Berl), 2021, 99(5): 699-711. PMID: 33517471. PMCID: PMC8055636. DOI: 10.1007/s00109-021-02036-8.
5 Martin A, David V, Quarles LD. Regulation and function of the FGF23/klotho endocrine pathways[J]. Physiol Rev, 2012, 92(1): 131-155. PMID: 22298654. PMCID: PMC3306265. DOI: 10.1152/physrev.00002.2011.
6 Kurosu H, Ogawa Y, Miyoshi M, et al. Regulation of fibroblast growth factor-23 signaling by klotho[J]. J Biol Chem, 2006, 281(10): 6120-6123. PMID: 16436388. PMCID: PMC2637204. DOI: 10.1074/jbc.C500457200.
7 Sp?th SS, Andrade AC, Chau M, et al. Local regulation of growth plate cartilage[J]. Endocr Dev, 2011, 21: 12-22. PMID: 21865750. DOI: 10.1159/000328084.
8 Xie Y, Zhou S, Chen H, et al. Recent research on the growth plate: advances in fibroblast growth factor signaling in growth plate development and disorders[J]. J Mol Endocrinol, 2014, 53(1): T11-T34. PMID: 25114206. DOI: 10.1530/JME-14-0012.
9 中华医学会儿科学分会肾脏学组. 儿童激素敏感、复发/依赖肾病综合征诊治循证指南（2016）[J]. 中华儿科杂志, 2017, 55(10): 729-734. PMID: 29050108. DOI: 10.3760/cma.j.issn.0578-1310.2017.10.003.
10 李辉, 季成叶, 宗心南, 等. 中国0~18岁儿童、青少年身高、体重的标准化生长曲线[J]. 中华儿科杂志, 2009, 47(7): 487-492. PMID: 19951507. DOI: 10.3760/cma.j.issn.0578-1310.2009.07.003.
11 张绍岩, 刘丽娟, 吴真列, 等. 中国人手腕骨发育标准：中华05 I.TW3-CRUS、TW3-C腕骨和RUS-CHN方法[J]. 中国运动医学杂志, 2006, 25(5): 509-516. DOI: 10.3969/j.issn.1000-6710.2006.05.001.
12 Tang Y, Hou L, Sun T, et al. Improved equations to estimate GFR in Chinese children with chronic kidney disease[J]. Pediatr Nephrol, 2023, 38(1): 237-247. PMID: 35467153. DOI: 10.1007/s00467-022-05552-y.
13 Raimann A, Ertl DA, Helmreich M, et al. Fibroblast growth factor 23 and Klotho are present in the growth plate[J]. Connect Tissue Res, 2013, 54(2): 108-117. PMID: 23206185. DOI: 10.3109/03008207.2012.753879.
14 Su N, Jin M, Chen L. Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models[J]. Bone Res, 2014, 2: 14003. PMID: 26273516. PMCID: PMC4472122. DOI: 10.1038/boneres.2014.3.
15 Powers CJ, McLeskey SW, Wellstein A. Fibroblast growth factors, their receptors and signaling[J]. Endocr Relat Cancer, 2000, 7(3): 165-197. PMID: 11021964. DOI: 10.1677/erc.0.0070165.
16 Stanczyk M, Chrul S, Wyka K, et al. Serum intact fibroblast growth factor 23 in healthy paediatric population[J]. Open Med (Wars), 2021, 16(1): 1022-1027. PMID: 34258392. PMCID: PMC8262519. DOI: 10.1515/med-2021-0288.
17 崔岭, 韦洪艳, 张慧儒, 等. 慢性肾衰患者血清FGF-23、Klotho蛋白水平与疾病严重程度的关系[J]. 河北医药, 2023, 45(12): 1828-1831. DOI: 10.3969/j.issn.1002-7386.2023.12.015.
18 Jennette JC, Olson JL, Silva FG, et al. Heptinstall's Pathology of the Kidney[M]. 7th ed. Amsterdam: Wolters Kluwer Health, 2014: 125-154.
PDF(786 KB)
