骨保护素/RANKL 轴与血液透析患者冠状动脉钙化进展。
Osteoprotegerin/RANKL axis and progression of coronary artery calcification in hemodialysis patients.
机构信息
Istanbul Faculty of Medicine, Department of Internal Medicine and Nephrology, Istanbul University, Istanbul, Turkey.
出版信息
Clin J Am Soc Nephrol. 2012 Jun;7(6):965-73. doi: 10.2215/CJN.11191111. Epub 2012 Apr 5.
BACKGROUND AND OBJECTIVES
Vascular calcification is associated with increased cardiovascular mortality in chronic hemodialysis patients. This prospective study investigated the relationship between serum osteoprotegerin, receptor activator of NF-κB ligand, inflammatory markers, and progression of coronary artery calcification score.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventy-eight hemodialysis patients were enrolled. Serum IL-1β, IL-6, TNF-α, osteoprotegerin, receptor activator of NF-κB, fetuin A, and bone alkaline phosphatase were measured by ELISA. Coronary artery calcification score was measured two times with 1-year intervals, and patients were classified as progressive or nonprogressive.
RESULTS
Baseline and first-year serum osteoprotegerin levels were significantly higher in the progressive than nonprogressive group (17.39±9.67 versus 12.90±6.59 pmol/L, P=0.02; 35.17±18.35 versus 24±11.65 pmol/L, P=0.002, respectively). The ratio of serum osteoprotegerin to receptor activator of NF-κB ligand at 1 year was significantly higher in the progressive group (0.26 [0.15-0.46] versus 0.18 [0.12-0.28], P=0.004). Serum osteoprotegerin levels were significantly correlated with coronary artery calcification score at both baseline (r=0.36, P=0.001) and 1 year (r=0.36, P=0.001). Importantly, progression in coronary artery calcification score significantly correlated with change in serum osteoprotegerin levels (r=0.39, P=0.001). In addition, serum receptor activator of NF-κB ligand levels were significantly inversely correlated with coronary artery calcification scores at both baseline (r=-0.29, P=0.01) and 1 year (r=-0.29, P=0.001). In linear regression analysis for predicting coronary artery calcification score progression, only baseline coronary artery calcification score and change in osteoprotegerin were retained as significant factors in the model.
CONCLUSIONS
Baseline coronary artery calcification score and serum osteoprotegerin levels were significantly associated with progression of coronary artery calcification score in hemodialysis patients.
背景与目的
血管钙化与慢性血液透析患者心血管死亡率的增加有关。本前瞻性研究旨在探讨血清护骨素、核因子-κB 受体激活剂配体、炎症标志物与冠状动脉钙化评分进展的关系。
设计、地点、参与者和测量：共纳入 78 例血液透析患者。采用 ELISA 法检测血清白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α、护骨素、核因子-κB 受体激活剂、胎球蛋白 A 和骨碱性磷酸酶。冠状动脉钙化评分在 1 年内进行两次测量，患者分为进展组和非进展组。
结果
基线和第 1 年时，进展组的血清护骨素水平明显高于非进展组（17.39±9.67 比 12.90±6.59 pmol/L，P=0.02；35.17±18.35 比 24±11.65 pmol/L，P=0.002）。进展组第 1 年时血清护骨素与核因子-κB 受体激活剂配体的比值明显较高（0.26[0.15-0.46]比 0.18[0.12-0.28]，P=0.004）。血清护骨素水平与基线时（r=0.36，P=0.001）和第 1 年时（r=0.36，P=0.001）的冠状动脉钙化评分均显著相关。重要的是，冠状动脉钙化评分的进展与血清护骨素水平的变化显著相关（r=0.39，P=0.001）。此外，血清核因子-κB 受体激活剂配体水平与基线时（r=-0.29，P=0.01）和第 1 年时（r=-0.29，P=0.001）的冠状动脉钙化评分均显著负相关。在冠状动脉钙化评分进展的线性回归分析中，只有基线时的冠状动脉钙化评分和护骨素的变化被保留为模型中的显著因素。
结论
基线时的冠状动脉钙化评分和血清护骨素水平与血液透析患者冠状动脉钙化评分的进展显著相关。
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