Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis:: a cross-sectional study
Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis:: a cross-sectional study
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DOI：
10.1016/s0140-6736(03)12710-9
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发表时间：
2003-03-08
期刊：
影响因子：
168.9
通讯作者：
Floege, J
中科院分区：
文献类型：
--
作者：
Ketteler, M;Bongartz, P;Floege, J
背景血管钙化是尿毒症患者最突出的潜在病理学发现，也是一个预测因素。的死亡率。胎球蛋白-A（α（2）-Heremans Schmid糖蛋白; AHSG）是体内钙化的重要循环抑制剂，在急性期反应中下调。我们的目的是调查的假设，AHSG缺乏症是直接相关的尿毒症vascular calcium.Methods我们做了一个横断面研究，在312例稳定的血液透析患者分析AHSG和C-反应蛋白（CRP）的相互关系和他们的预测效果的全因和心血管死亡率，在一个为期32个月。随后，我们测试了血清抑制长期透析患者（n=17）明显软组织钙化的CaxPO（4）沉淀的能力，短期透析患者（n=8）无钙化和心血管疾病证据。结果血液透析患者血清AHSG浓度显著降低（平均0.66 g/L [SD 0.28]）比健康对照组（0.72 [0.19]）。低浓度的糖蛋白与CRP水平升高、心血管（p=0.031）和全因死亡率（p=0.0013）增加相关。低AHSG浓度的长期透析患者的血清显示出体外抑制CaxPO（4）沉淀的能力受损（平均IC 50：9.0穆尔血清[SD 3.1] vs短期透析患者7.5 [0.8]和对照组6.4 [2.6]）。用纯化的AHSG重建血清使这种损害恢复正常。解释AHSG缺乏与炎症有关，并将血管钙化与透析患者的死亡率联系起来。急性期反应的激活和AHSG缺乏可能是尿毒症患者动脉粥样硬化加速的原因。
Background Vascular calcification is the most prominent underlying pathological finding in patients with uraemia, and is a predictor. of mortality in this population. Fetuin-A (alpha(2)-Heremans Schmid glycoprotein; AHSG) is an important circulating inhibitor of calcification in vivo, and is downregulated during the acute-phase response. We aimed to investigate the hypothesis that AHSG deficiency is directly related to uraemic vascular calcification.Methods We did a cross-sectional study in 312 stable patients on haemodialysis to analyse the inter-relation of AHSG and C-reactive protein (CRP) and their predictive effect on all-cause and cardiovascular mortality, over a period of 32 months. Subsequently, we tested the capacity of serum to inhibit CaxPO(4) precipitation in patients on long-term dialysis (n=17) with apparent soft-tissue calcifications, and in those on short-term dialysis (n=8) without evidence of calcifications and cardiovascular disease.Findings AHSG concentrations in serum were significantly lower in patients on haemodialysis (mean 0.66 g/L [SD 0.28]) than in healthy controls (0.72 [0.19]). Low concentrations of the glycoprotein were associated with raised amounts of CRP and with enhanced cardiovascular (p=0.031) and all-cause mortality (p=0.0013). Sera from patients on long-term dialysis with low AHSG concentrations showed impaired ex-vivo capacity to inhibit CaxPO(4) precipitation (mean IC50: 9.0 muL serum [SD 3.1] vs 7.5 [0.8] in short-term patients and 6.4 [2.6] in controls). Reconstitution of sera with purified AHSG returned this impairment to normal.Interpretation AHSG deficiency is associated with inflammation and links vascular calcification to mortality in patients on dialysis. Activated acute-phase response and AHSG deficiency might account for accelerated atherosclerosis in uraemia.