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补充胆钙化醇对慢性肾病儿童铁调素影响的初步研究:D-fense试验结果

Pilot study of the effect of cholecalciferol supplementation on hepcidin in children with chronic kidney disease: Results of the D-fense Trial.

作者信息

Atkinson Meredith A, Juraschek Stephen P, Bertenthal Michael S, Detrick Barbara, Furth Susan L, Miller Edgar R

机构信息

Division of Pediatric Nephrology, Johns Hopkins University School of Medicine, 200 N. Wolfe St., Baltimore, MD, 21287, USA.

Johns Hopkins University School of Medicine, Baltimore, MD, USA.

出版信息

Pediatr Nephrol. 2017 May;32(5):859-868. doi: 10.1007/s00467-016-3563-6. Epub 2016 Dec 24.

Abstract

BACKGROUND

Hepcidin is a key mediator of the anemia of chronic kidney disease (CKD). There is emerging evidence that 25-hydroxyvitamin D (25D) regulates hepcidin production.

METHODS

A randomized controlled trial of daily vitamin D supplementation for 12 weeks was performed with the aim to test the effects of 4000 versus 400 IU of cholecalciferol on serum hepcidin levels in children with non-dialysis CKD recruited at a tertiary care children's hospital. Hepcidin was quantified using a validated competitive enzyme-linked immunosorbent assay. 25D levels were measured using the chemiluminescence Liaison 25(OH)D assay system. Co-variables included hemoglobin, C-reactive protein, ferritin, and serum calcium and phosphorus for safety monitoring.

RESULTS

A total of 34 subjects were randomized to either the intervention or control group, of whom 26.5% were female and 23.5% were African American. The mean age of the study cohort was 10.9 [standard deviation (SD) 5.8] years, the mean baseline glomerular filtration rate was 60 (SD 17.6) ml/min/1.73 m, and mean baseline 25D level was 29.7 (SD 11.5) ng/ml. At baseline, 50% of subjects were 25D deficient. There were no significant differences in baseline characteristics between the intervention and control groups. Treatment with 4000 IU cholecalciferol was not associated with significant change in hepcidin level at 4 or 12 weeks, and multivariable generalized estimating equation regression demonstrated no significant difference in change in hepcidin over the treatment period in either arm. The median C-reactive protein level decreased significantly at 12 weeks in the intervention group.

CONCLUSIONS

These results do not suggest that daily nutritional vitamin D supplementation modifies serum hepcidin levels in children with CKD. Further study will be required to determine whether supplementation may be effective in children with more advanced CKD or those on dialysis.

摘要

背景

铁调素是慢性肾脏病(CKD)贫血的关键介质。越来越多的证据表明,25-羟基维生素D(25D)可调节铁调素的产生。

方法

进行了一项为期12周的每日补充维生素D的随机对照试验,目的是测试4000国际单位与400国际单位胆钙化醇对一家三级儿童医院招募的非透析CKD儿童血清铁调素水平的影响。使用经过验证的竞争性酶联免疫吸附测定法定量铁调素。使用化学发光Liaison 25(OH)D测定系统测量25D水平。协变量包括血红蛋白、C反应蛋白、铁蛋白以及血清钙和磷,用于安全监测。

结果

共有34名受试者被随机分为干预组或对照组,其中26.5%为女性,23.5%为非裔美国人。研究队列的平均年龄为10.9岁[标准差(SD)5.8],平均基线肾小球滤过率为60(SD 17.6)ml/min/1.73m²,平均基线25D水平为29.7(SD 11.5)ng/ml。基线时,50%的受试者存在25D缺乏。干预组和对照组的基线特征无显著差异。4000国际单位胆钙化醇治疗在4周或12周时与铁调素水平的显著变化无关,多变量广义估计方程回归显示,两组在治疗期间铁调素变化均无显著差异。干预组在12周时C反应蛋白水平中位数显著下降。

结论

这些结果并不表明每日补充营养性维生素D会改变CKD儿童的血清铁调素水平。需要进一步研究以确定补充维生素D对更晚期CKD儿童或透析儿童是否有效。

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