肾磷阈在儿童X-连锁低磷性佝偻病诊治中的临床价值

doi:10.7499/j.issn.1008-8830.2401056

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摘要目的探讨肾磷阈，即肾小管最大磷重吸收率与肾小球滤过率的比值（ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate, TmP/GFR）在X-连锁低磷性佝偻病（X-linked hypophosphatemic rickets, XLH）患儿诊治中的临床价值。方法回顾性纳入2010年1月—2023年1月在南京医科大学附属儿童医院初诊为XLH的83例患儿，收集初诊及随访数据，探讨TmP/GFR与佝偻病严重程度、钙磷代谢指标及磷酸盐治疗量的相关性。根据是否发生肾钙质沉着症将患儿分为肾钙质沉着组（n=47）和非肾钙质沉着组（n=36），比较两组患儿的临床资料。采用多因素logistic回归分析探讨XLH患儿并发肾钙质沉着症的影响因素。使用受试者操作特征曲线（receiver operating characteristic curve, ROC曲线）评估TmP/GFR对XLH患儿并发肾钙质沉着症的预测价值。结果 83例 XLH 患儿初诊时TmP/GFR为（0.78±0.21）mmol/L，个体差异很大（范围：0.28~1.24 mmol/L）。TmP/GFR与XLH患儿佝偻病严重程度无显著相关性（P>0.05）。甲状旁腺激素与TmP/GFR呈负相关（r_s=-0.020，P=0.008），血磷（r_s=0.384，P<0.001）、血钙（r_s=0.251，P<0.001）及25羟维生素D（r_s=0.179，P<0.001）与TmP/GFR呈正相关，TmP/GFR与碱性磷酸酶（r_s=-0.002，P=0.960）及磷元素治疗剂量（r_s=0.012，P=0.800）无显著相关性。肾钙质沉着组的血钙和TmP/GFR均明显低于非肾钙质沉着组（P<0.05），而甲状旁腺激素和尿钙浓度均明显高于非肾钙质沉着组（P<0.05）。多因素logistic回归分析显示，TmP/GFR和尿钙浓度与XLH患儿并发肾钙质沉着症密切相关（P<0.05）。ROC曲线分析显示，TmP/GFR、尿钙浓度以及两者联合检测预测XLH患儿并发肾钙质沉着症的曲线下面积分别为0.696、0.679、0.761。结论 TmP/GFR可以作为诊断儿童XLH的一项重要指标，然而它并不具备反映佝偻病严重程度及活动性的能力，无法作为判断传统治疗疗效的指标。尿钙浓度和TmP/GFR对XLH患儿并发肾钙质沉着症具有良好的预测价值，可为临床评估XLH患儿发生肾钙质沉着症的风险提供参考。

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关键词 ： X-连锁低磷性佝偻病, 肾磷阈, 肾钙质沉着症, 儿童

Abstract：Objective To explore the clinical value of the renal phosphorus threshold (ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate, TmP/GFR) in the diagnosis and treatment of children with X-linked hypophosphatemic rickets (XLH). Methods A retrospective study was conducted, including 83 children diagnosed with XLH at Children's Hospital of Nanjing Medical University from January 2010 to January 2023. Initial diagnosis and follow-up data were collected to investigate the correlation of TmP/GFR with the severity of rickets, calcium and phosphorus metabolism indicators, and the dosage of phosphate treatment. Children were divided into two groups based on the occurrence of renal calcification: the renal calcification group (n=47) and the non-renal calcification group (n=36). Clinical data between the two groups were compared. Multivariate logistic regression analysis was used to identify factors influencing renal calcification in XLH children. The predictive value of TmP/GFR for renal calcification in XLH children was evaluated using receiver operating characteristic (ROC) curves. Results In the 83 XLH children, the initial TmP/GFR was (0.78±0.21) mmol/L, with significant individual variation (range: 0.28-1.24 mmol/L). TmP/GFR showed no significant correlation with the severity of rickets (P>0.05). Parathyroid hormone was negatively correlated with TmP/GFR (r_s=-0.020, P=0.008), while blood phosphorus (r_s=0.384, P<0.001), blood calcium (r_s=0.251, P<0.001), and 25-hydroxyvitamin D (r_s=0.179, P<0.001) were positively correlated with TmP/GFR. No significant correlation was found between TmP/GFR and alkaline phosphatase (r_s=-0.002, P=0.960) or phosphate treatment dosage (r_s=0.012, P=0.800). Blood calcium and TmP/GFR levels were significantly lower in the renal calcification group than in the non-renal calcification group (P<0.05), while parathyroid hormone and urine calcium levels were significantly higher in the renal calcification group (P<0.05). Multivariate logistic regression analysis indicated that TmP/GFR and urine calcium levels were closely associated with renal calcification in XLH children (P<0.05). ROC curve analysis revealed that the areas under the curve for TmP/GFR, urine calcium, and their combined detection predicting renal calcification in XLH children were 0.696, 0.679, and 0.761, respectively. Conclusions TmP/GFR may serve as an important diagnostic indicator for pediatric XLH; however, it does not reflect the severity or activity of rickets and cannot be used to judge the efficacy of traditional treatment. Urine calcium and TmP/GFR are valuable predictors for renal calcification in XLH children.

Key words： X-linked hypophosphatemic rickets Renal phosphorus threshold Renal calcification Child

收稿日期: 2024-01-15

通讯作者: 陈颖，女，主任医师。Email：xych0929@sina.com。 E-mail: xych0929@sina.com

作者简介: 陶佳琪，女，硕士研究生；

引用本文:

陶佳琪,陈颖. 肾磷阈在儿童X-连锁低磷性佝偻病诊治中的临床价值[J]. 中国当代儿科杂志, 2024, 26(9): 926-932.

TAO Jia-Qi,CHEN Ying. Clinical value of renal phosphorus threshold in the diagnosis and treatment X-linked hypophosphatemic rickets in children[J]. CJCP, 2024, 26(9): 926-932.

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	Carpenter TO, Imel EA, Holm IA, et al. A clinician's guide to X-linked hypophosphatemia[J]. J Bone Miner Res, 2011, 26(7): 1381-1388. PMID: 21538511. PMCID: PMC3157040. DOI: 10.1002/jbmr.340.
	Kinoshita Y, Fukumoto S. X-linked hypophosphatemia and FGF23-related hypophosphatemic diseases: prospect for new treatment[J]. Endocr Rev, 2018, 39(3): 274-291. PMID: 29381780. DOI: 10.1210/er.2017-00220.
	Imel EA, Glorieux FH, Whyte MP, et al. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial[J]. Lancet, 2019, 393(10189): 2416-2427. PMID: 31104833. PMCID: PMC7179969. DOI: 10.1016/S0140-6736(19)30654-3.
	Bijvoet OL. Relation of plasma phosphate concentration to renal tubular reabsorption of phosphate[J]. Clin Sci, 1969, 37(1): 23-36. PMID: 5822530.
	5 邱明才, 戴晨琳. 代谢性骨病学[M]. 北京: 人民卫生出版社, 2012: 356-357.
	中华医学会儿科学分会内分泌遗传代谢学组, 中国罕见病联盟, 中华儿科杂志编辑委员会. 儿童X连锁低磷性佝偻病诊治与管理专家共识[J]. 中华儿科杂志, 2022, 60(6): 501-506. PMID: 35658353. DOI: 10.3760/cma.j.cn112140-20220223-00141.
	Kruse K, Hinkel GK, Griefahn B. Calcium metabolism and growth during early treatment of children with X-linked hypophosphataemic rickets[J]. Eur J Pediatr, 1998, 157(11): 894-900. PMID: 9835432. DOI: 10.1007/s004310050962.
	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.
	9 江载芳, 申昆玲, 沈颖, 等. 诸福棠实用儿科学[M]. 8版. 北京: 人民卫生出版社, 2015: 561-562.
	10 中华人民共和国国家卫生健康委员会. 儿童临床常用生化检验项目参考区间: WS/T 780-2021[S]. 北京: 中国标准出版社, 2021.
	Walton RJ, Bijvoet OL. Nomogram for derivation of renal threshold phosphate concentration[J]. Lancet, 1975, 2(7929): 309-310. PMID: 50513. DOI: 10.1016/s0140-6736(75)92736-1.
	Hamdy NAT, Harvengt P, Usardi A. X-linked hypophosphatemia: the medical expert's challenges and the patient's concerns on their journey with the disease[J]. Arch Pediatr, 2021, 28(7): 612-618. PMID: 34593293. DOI: 10.1016/j.arcped.2021.09.005.
	Guven A, Al-Rijjal RA, BinEssa HA, et al. Mutational analysis of PHEX, FGF23 and CLCN5 in patients with hypophosphataemic rickets[J]. Clin Endocrinol (Oxf), 2017, 87(1): 103-112. PMID: 28383812. DOI: 10.1111/cen.13347.
	Beck-Nielsen SS, Brixen K, Gram J, et al. Mutational analysis of PHEX, FGF23, DMP1, SLC34A3 and CLCN5 in patients with hypophosphatemic rickets[J]. J Hum Genet, 2012, 57(7): 453-458. PMID: 22695891. DOI: 10.1038/jhg.2012.56.
	Haffner D, Emma F, Eastwood DM, et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia[J]. Nat Rev Nephrol, 2019, 15(7): 435-455. PMID: 31068690. PMCID: PMC7136170. DOI: 10.1038/s41581-019-0152-5.
	Payne RB. Renal tubular reabsorption of phosphate (TmP/GFR): indications and interpretation[J]. Ann Clin Biochem, 1998, 35 (Pt 2): 201-206. PMID: 9547891. DOI: 10.1177/000456329803500203.
	Wang S, Wang X, He M, et al. Efficacy and safety of burosumab in X-linked hypophosphatemia[J]. J Clin Endocrinol Metab, 2023, 109(1): 293-302. PMID: 37497620. DOI: 10.1210/clinem/dgad440.
	Derain Dubourg L, Aurelle M, Chardon L, et al. Tubular phosphate handling: references from child to adulthood in the era of standardized serum creatinine[J]. Nephrol Dial Transplant, 2022, 37(11): 2150-2156. PMID: 34850142. DOI: 10.1093/ndt/gfab331.
	Holm IA, Nelson AE, Robinson BG, et al. Mutational analysis and genotype-phenotype correlation of the PHEX gene in X-linked hypophosphatemic rickets[J]. J Clin Endocrinol Metab, 2001, 86(8): 3889-3899. PMID: 11502829. DOI: 10.1210/jcem.86.8.7761.
	Igaki JM, Yamada M, Yamazaki Y, et al. High iFGF23 level despite hypophosphatemia is one of the clinical indicators to make diagnosis of XLH[J]. Endocr J, 2011, 58(8): 647-655. PMID: 21597229. DOI: 10.1507/endocrj.k10e-257.
	21 张丛, 赵真, 许莉军, 等. X-连锁显性低血磷性佝偻病/骨软化症患者血清成纤维细胞生长因子23水平[J]. 中华骨质疏松和骨矿盐疾病杂志, 2019, 12(1): 24-31. DOI: 10.3969/j.issn.1674-2591.2019.01.003.
	Keskin M, Sava?-Erdeve ?, Sa?sak E, et al. Risk factors affecting the development of nephrocalcinosis, the most common complication of hypophosphatemic rickets[J]. J Pediatr Endocrinol Metab, 2015, 28(11-12): 1333-1337. PMID: 26203600. DOI: 10.1515/jpem-2014-0447.
	23 汪伶伶, 吴光驰. 低磷酸盐性佝偻病30例[J]. 实用儿科临床杂志, 2006, 21(14): 929-930, 932. DOI: 10.3969/j.issn.1003-515X.2006.14.022.
	Carpenter TO. New perspectives on the biology and treatment of X-linked hypophosphatemic rickets[J]. Pediatr Clin North Am, 1997, 44(2): 443-466. PMID: 9130929. DOI: 10.1016/s0031-3955(05)70485-5.
	Dhayat NA, Lüthi D, Schneider L, et al. Distinct phenotype of kidney stone formers with renal phosphate leak[J]. Nephrol Dial Transplant, 2019, 34(1): 129-137. PMID: 29939320. DOI: 10.1093/ndt/gfy170.