肾磷阈在儿童X-连锁低磷性佝偻病诊治中的临床价值

Clinical value of renal phosphorus threshold in the diagnosis and treatment X-linked hypophosphatemic rickets in children

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。

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.