The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis
The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis
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DOI：
10.1093/ndt/gfn226
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发表时间：
2008-10-01
影响因子：
6.1
通讯作者：
Rees, Lesley
中科院分区：
文献类型：
--
作者：
Shroff, Rukshana C.;Shah, Vanita;Rees, Lesley
背景资料。血管钙化发生在大多数慢性肾脏疾病患者中，但一小部分患者即使暴露在类似的尿毒症环境中也不会发生钙化。生理性钙化抑制剂胎球蛋白-A、骨保护素(OPG)和欠羧化基质GLA蛋白(UC-MGP)可能在预防异位钙化的发生和发展中发挥作用，但临床研究缺乏且相互矛盾的数据。对61例透析患儿进行胎球蛋白-A、骨钙素、UC-MGP检测，并探讨其与临床、生化及血管指标的关系。透析患者血清胎球蛋白-A和骨钙素水平高于对照组，而UC-MGP水平低于对照组。在对照组中，胎球蛋白-A和OPG随年龄增长而增加。胎球蛋白A与透析年限(P=0.0013)、平均时间血磷(P=0.03)、超敏C反应蛋白(P=0.001)呈负相关。主动脉脉搏波速度(PWV)、增大指数与胎球蛋白-A呈负相关，与PWV、OPG呈正相关。钙化组胎球蛋白A低于非钙化组，OPG高于非钙化组。在多元线性回归分析中，胎球蛋白A独立预测主动脉PWV(P=0.004.0 2，ss=-0.45，模型R2=48%)，胎球蛋白A和骨钙素预测心脏钙化(P=0.0 2，ss=-0.2 9和P=0.014，ss=0.33，模型R2=32%)。这是第一项确定儿童钙化抑制物正常水平的研究，并表明胎球蛋白-A和OPG与透析儿童血管僵硬和钙化增加有关。儿童体内较高的胎球蛋白-A水平表明，在有利于钙化和促炎的尿毒症环境中暴露的早期阶段，胎球蛋白-A可能具有保护性上调。
Background. Vascular calcification occurs in the majority of patients with chronic kidney disease, but a subset of patients does not develop calcification despite exposure to a similar uraemic environment. Physiological inhibitors of calcification, fetuin-A, osteoprotegerin (OPG) and undercarboxylated-matrix Gla protein (uc-MGP) may play a role in preventing the development and progression of ectopic calcification, but there are scarce and conflicting data from clinical studies.Methods. We measured fetuin-A, OPG and uc-MGP in 61 children on dialysis and studied their associations with clinical, biochemical and vascular measures.Results. Fetuin-A and OPG were higher and uc-MGP lower in dialysis patients than controls. In controls, fetuin-A and OPG increased with age. Fetuin-A showed an inverse correlation with dialysis vintage (P = 0.0013), time-averaged serum phosphate (P = 0.03) and hs-CRP (P = 0.001). Aortic pulse wave velocity (PWV) and augmentation index showed a negative correlation with fetuin-A while a positive correlation was seen with PWV and OPG. Patients with calcification had lower fetuin-A and higher OPG than those without calcification. On multiple linear regression analysis Fetuin-A independently predicted aortic PWV (P = 0.004, ss = -0.45, model R-2 = 48%) and fetuin-A and OPG predicted cardiac calcification (P = 0.02, ss = -0.29 and P = 0.014, ss = 0.33, respectively, model R-2 = 32%).Conclusions. This is the first study to define normal levels of the calcification inhibitors in children and show that fetuin-A and OPG are associated with increased vascular stiffness and calcification in children on dialysis. Higher levels of fetuin-A in children suggest a possible protective upregulation of fetuin-A in the early stages of exposure to the pro-calcific and pro-inflammatory uraemic environment.