背景:成纤维细胞生长因子23(FGF23)是一种骨源性激素,在慢性肾脏病-矿物质骨紊乱中起重要作用,并与CKD进展和心血管疾病相关。CKD相关性贫血相关因素,包括缺铁,可以提高FGF23产量。这项研究旨在评估贫血和/或铁缺乏是否与FGF23的循环浓度增加有关。特征明确的儿童慢性肾脏病(CGID)研究队列。
方法:血红蛋白浓度,铁参数,C-末端(总)FGF23、完整FGF23和相关的辅助变量在CMiD研究受试者的横断面分析中测量。
结果:在493名CKD儿科患者(中位[四分位距]13[9,16]岁)中,估计肾小球滤过率中位数为48[35,61]ml/min/1.73m2,103例患者(21%)贫血.贫血受试者的总FGF23浓度高于非贫血受试者(204[124,390]vs.109[77,168]RU/ml,p<0.001)。在多变量线性回归建模中,在调整人口统计学指标后,贫血与较高的总FGF23独立相关,与肾脏有关,矿物质代谢,和炎症协变量(标准化β(95%置信区间)0.10(0.04,0.17),p=0.002)。在具有可用铁参数的受试者的子集中(n=191),铁缺乏与FGF23总浓度显著升高无关.在测量了总FGF23和完整FGF23的亚组(n=185)中,在完全调整的模型中,贫血与较高的总FGF23(标准化β(95%CI)0.16(0.04,0.27),p=0.008),但不完整的FGF23(标准化β(95%CI)0.02(-0.12,0.15),p=0.81)。
结论:在这个CKD患儿队列中,贫血与总FGF23水平升高相关,但与完整FGF23升高无关,提示可能对FGF23的产生和切割均有影响.需要进一步的研究来研究影响CKD中FGF23产生和代谢的非矿物质因素。更高分辨率版本的图形摘要可作为补充信息。
BACKGROUND: Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a central role in chronic kidney disease-mineral bone disorder and is associated with CKD progression and cardiovascular morbidity. Factors related to CKD-associated anemia, including iron deficiency, can increase FGF23 production. This
study aimed to assess whether anemia and/or iron deficiency are associated with increased circulating concentrations of FGF23 in the large, well-characterized Chronic Kidney Disease in Children (CKiD)
study cohort.
METHODS: Hemoglobin concentrations, iron parameters, C-terminal (total) FGF23, intact FGF23, and relevant covariables were measured in cross-sectional analysis of CKiD
study subjects.
RESULTS: In 493 pediatric patients with CKD (median [interquartile range] age 13 [9, 16] years), the median estimated glomerular filtration rate was 48 [35, 61] ml/min/1.73 m2, and 103 patients (21%) were anemic. Anemic subjects had higher total FGF23 concentrations than non-anemic subjects (204 [124, 390] vs. 109 [77, 168] RU/ml, p < 0.001). In multivariable linear regression modeling, anemia was independently associated with higher total FGF23, after adjustment for demographic, kidney-related, mineral metabolism, and inflammatory covariables (standardized β (95% confidence interval) 0.10 (0.04, 0.17), p = 0.002). In the subset of subjects with available iron parameters (n = 191), iron deficiency was not associated with significantly higher total FGF23 concentrations. In the subgroup that had measurements of both total and intact FGF23 (n = 185), in fully adjusted models, anemia was significantly associated with higher total FGF23 (standardized β (95% CI) 0.16 (0.04, 0.27), p = 0.008) but not intact FGF23 (standardized β (95% CI) 0.02 (-0.12, 0.15), p = 0.81).
CONCLUSIONS: In this cohort of pediatric patients with CKD, anemia was associated with increased total FGF23 levels but was not independently associated with elevated intact FGF23, suggesting possible effects on both FGF23 production and cleavage. Further studies are warranted to investigate non-mineral factors affecting FGF23 production and metabolism in CKD.