Background

Mineral and bone disorder (MBD) and growth impairment are common complications of pediatric chronic kidney disease (CKD). Chronic inflammation detrimentally affects bone health and statural growth in non-CKD settings, but the impact of inflammation on CKD-MBD and growth in pediatric CKD remains poorly understood. This study assessed associations between inflammatory cytokines with biomarkers of CKD-MBD and statural growth in pediatric CKD.

Methods

This is a cross-sectional study of children with predialysis CKD stages II–V. Cytokines (IL-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, interferon-γ), bone alkaline phosphatase (BAP), and procollagen type 1 N-terminal propeptide (P1NP) were measured at the same time as standard CKD-MBD biomarkers. Associations between cytokines, CKD-MBD biomarkers, and height z-score were assessed using linear regression analysis.

Results

Among 63 children, 52.4% had stage 3 CKD, 76.2% non-glomerular CKD etiology, and 21% short stature. TNF-α was the only cytokine associated with parathyroid hormone (PTH) independent of glomerular filtration rate. After stratification by low, medium, and high TNF-α tertiles, significant differences in PTH, serum phosphorus, alkaline phosphatase, BAP, P1NP, and height z-score were found. In a multivariate analysis, TNF-α positively associated with phosphorus, PTH, and alkaline phosphatase and inversely associated with height z-score, independent of kidney function, age, sex, and active vitamin D analogue use.

Conclusions

TNF-α is positively associated with biomarkers of CKD-MBD and inversely associated with height z-score, indicating that inflammation likely contributes to the development of CKD-MBD and growth impairment in pediatric CKD. Prospective studies to definitively assess causative effects of inflammation on bone health and growth in children with CKD are warranted.

中文翻译：

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肿瘤坏死因子-α与慢性肾病儿童的矿物质骨紊乱和生长障碍有关

背景

矿物质和骨骼疾病 (MBD) 和生长障碍是小儿慢性肾脏病 (CKD) 的常见并发症。慢性炎症对非 CKD 环境中的骨骼健康和身材生长产生不利影响，但炎症对 CKD-MBD 和儿童 CKD 生长的影响仍然知之甚少。本研究评估了炎性细胞因子与 CKD-MBD 生物标志物与儿童 CKD 身高增长之间的关联。

方法

这是一项针对透析前 CKD II-V 期儿童的横断面研究。细胞因子（IL-1b、IL-4、IL-6、IL-8、IL-10、IL-12、IL-13、TNF-α、干扰素-γ）、骨碱性磷酸酶 (BAP) 和 1 型前胶原N-末端前肽 (P1NP) 与标准 CKD-MBD 生物标志物同时测量。使用线性回归分析评估细胞因子、CKD-MBD 生物标志物和身高z分数之间的关联。

结果

在 63 名儿童中，52.4% 为 3 期 CKD，76.2% 为非肾小球 CKD 病因，21% 为身材矮小。TNF-α 是唯一与甲状旁腺激素 (PTH) 相关的细胞因子，与肾小球滤过率无关。在按低、中、高 TNF-α 三分位数分层后，发现 PTH、血清磷、碱性磷酸酶、BAP、P1NP 和高度z值存在显着差异。在多变量分析中，TNF-α 与磷、PTH 和碱性磷酸酶呈正相关，与身高z评分呈负相关，与肾功能、年龄、性别和活性维生素 D 类似物的使用无关。

结论

TNF-α 与 CKD-MBD 的生物标志物呈正相关，与身高z评分呈负相关，表明炎症可能导致 CKD-MBD 的发展和儿童 CKD 的生长障碍。有必要进行前瞻性研究来明确评估炎症对 CKD 儿童骨骼健康和生长的影响。