肾移植患者颈动脉粥样硬化发展过程中的炎症、金属蛋白酶和生长因子
Inflammation, metalloproteinases, and growth factors in the development of carotid atherosclerosis in renal transplant patients.
作者信息
Sánchez-Escuredo A, Pastor M C, Bayés B, Morales-Indiano C, Troya M, Dolade M, Jimenez J A, Romero R, Lauzurica R
机构信息
Nephrology Department, Hospital Universitario Germans Trias I Pujol de Badalona, Universidad Autonoma de Barcelona, Barcelona Spain.
出版信息
Transplant Proc. 2010 Oct;42(8):2905-7. doi: 10.1016/j.transproceed.2010.07.076.
BACKGROUND
Cardiovascular disease is the leading cause of death in renal transplant (RT) patients. Both traditional and emerging risk factors, some of which are controversial, have been described in the pathogenesis of cardiovascular disease. Carotid ultrasound (CUS) is considered to be an excellent diagnostic tool for subclinical atherosclerosis.
OBJECTIVE
To evaluate the relationship between biomarkers of inflammation, growth factors, metalloproteinases, and the development of subclinical atherosclerosis diagnosed by using CUS.
METHODS
We studied 93 RT patients (aged 54±12 years; 67.9% men; 13.5% with pre-RT diabetes mellitus). The following biomarkers were determined in the patients' blood hours before RT: C-reactive protein (CRP) and serum amyloid A using nephelometry; interleukin (IL) 2, 6, 8, and 10 and soluble IL-2 receptor, tumor necrosis factor (TNF) α, vascular endothelial growth factor (VEGF), epidermal growth factor, and monocyte chemotactic peptide using chemoluminescence; and pregnancy-associated plasma protein (PAPP)A using ELISA. A CUS was carried out during the first month after RT.
RESULTS
Carotid intima-media thickness (IMT) was elevated in 51% of the patients, and 50.5% of the patients had atherosclerotic plaque. Both plaque (P=.004) and IMT (P=.001) correlated with age, and the increase of IMT was progressive, on both the left and the right side. Pre-RT CRP, IL-8, TNF-α, VEGF, MCP-1, and PAPP-A were significantly more elevated in patients with plaque. In the multivariate analysis adjusted for clinical variables, age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.10; P=.04), CRP (OR, 7.5; 95% CI, 2.05-27.3; P=.002), IL-8 (OR, 4.73; 95% CI, 1.27-17.6; P=.02), and PAPP-A (OR, 4.45; 95% CI, 1.22-16.2; P=.023) were independent markers of the presence of plaque.
CONCLUSIONS
Age, CRP, IL-8, and PAPP-A, and not growth factors, are markers of carotid atheromatous plaque in RT patients.
背景
心血管疾病是肾移植（RT）患者的主要死因。传统和新出现的危险因素在心血管疾病的发病机制中均有描述，其中一些存在争议。颈动脉超声（CUS）被认为是亚临床动脉粥样硬化的优秀诊断工具。
目的
评估炎症、生长因子、金属蛋白酶生物标志物与使用CUS诊断的亚临床动脉粥样硬化发展之间的关系。
方法
我们研究了93例RT患者（年龄54±12岁；67.9%为男性；13.5%有肾移植前糖尿病）。在肾移植前数小时测定患者血液中的以下生物标志物：采用散射比浊法测定C反应蛋白（CRP）和血清淀粉样蛋白A；采用化学发光法测定白细胞介素（IL）2、6、8和10以及可溶性IL-2受体、肿瘤坏死因子（TNF）α、血管内皮生长因子（VEGF）、表皮生长因子和单核细胞趋化肽；采用酶联免疫吸附测定法测定妊娠相关血浆蛋白（PAPP）A。在肾移植后第一个月进行颈动脉超声检查。
结果
51%的患者颈动脉内膜中层厚度（IMT）升高，50.5%的患者有动脉粥样硬化斑块。斑块（P = 0.004）和IMT（P = 0.001）均与年龄相关，且IMT的增加是渐进性的，双侧均如此。肾移植前CRP、IL-8、TNF-α、VEGF、单核细胞趋化蛋白-1（MCP-1）和PAPP-A在有斑块的患者中显著升高。在针对临床变量进行校正的多变量分析中，年龄（比值比[OR]，1.05；95%置信区间[CI]，1.01 - 1.10；P = 0.04）、CRP（OR，7.5；95% CI，2.05 - 27.3；P = 0.002）、IL-8（OR，4.73；95% CI, 1.27 - 17.6；P = 0.02）和PAPP-A（OR，4.45；95% CI，1.22 - 16.2；P = 0.023）是斑块存在的独立标志物。
结论
年龄、CRP、IL-8和PAPP-A而非生长因子是肾移植患者颈动脉粥样斑块的标志物。
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