Fine-tuning of the prediction of mortality in hemodialysis patients by use of cytokine proteomic determination
Fine-tuning of the prediction of mortality in hemodialysis patients by use of cytokine proteomic determination
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DOI：
10.2215/cjn.02010507
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发表时间：
2008-03-01
影响因子：
9.8
通讯作者：
Dupuy, Anne-Marie
中科院分区：
文献类型：
--
作者：
Badiou, Stephanie;Cristol, Jean-Paul;Dupuy, Anne-Marie
背景和目的：炎症诱导的动脉粥样硬化和对感染的易感性增强与免疫功能障碍有关，是血液透析患者死亡率的重要组成部分。这项为期4年的前瞻性研究旨在使用细胞因子蛋白质组学测定来预测血液透析患者的心血管和非心血管死亡率。设计、设置、参与者和测量：使用蛋白质组学生物芯片系统测量了134名稳定血液透析患者的12种细胞因子水平，并与150名健康志愿者的对照组进行了比较。采用Cox比例风险回归分析确定细胞因子与临床结局的关系。结果：与对照组相比，血液透析患者的促炎状态以抗炎/促炎细胞因子比值降低为特征。在对年龄、性别、吸烟和高敏c反应蛋白水平进行校正后，IL-6和(IL-4+IL-10)/IL-6比值与心血管死亡率的显著特异性增加相关（在比较第三和第一分位数时，风险比分别为11.32[95%可信区间2.52 ~ 50.90,P < 0.01]和3.14[95%可信区间1.20 ~ 8.22,P < 0.05]）。有趣的是，(IL-4+IL-6+IL-10)/(IL-2+ ifn - γ)比值，作为淋巴细胞T辅助亚群细胞因子分泌的标志，仅与非心血管死亡率相关（风险比4.93；95%可信区间1.03 ~ 23.65;P < 0.05）。结论：除了IL-6对心血管疾病死亡率的预测外，细胞因子比值的测定可用于识别血液透析患者非心血管疾病死亡率增加的风险。
Background and objectives: Inflammation-induced atherosclerosis and enhanced susceptibility to infection are linked to immune dysfunction and account for an important part of mortality in hemodialysis patients. This 4-yr prospective study aimed to use cytokine proteomic determination for predicting cardiovascular and noncardiovascular mortality in hemodialysis patients.Design, setting, participants, & measurements: Levels of 12 cytokines were measured using a proteomic biochip system in 134 patients who were on stable hemodialysis and compared with a control group of 150 healthy volunteers. Cox proportional hazards regression analysis was used to determine the relationship between cytokine and clinical outcome.Results: A proinflammatory state characterized by decreased anti-/proinflammatory cytokine ratio was evidenced in hemodialysis patients compared with control subjects. After adjustment for age, gender, smoking, and high-sensitivity C-reactive protein levels, IL-6 and (IL-4+IL-10)/IL-6 ratio were associated with a significant and specific enhanced hazard ratio of cardiovascular mortality (hazard ratio 11.32 [95% confidence interval 2.52 to 50.90; P < 0.01] and hazard ratio 3.14 [95% confidence interval 1.20 to 8.22; P < 0.05], respectively, when comparing the third and first tertiles). It is interesting that (IL-4+IL-6+IL-10)/(IL-2+IFN-gamma) ratio, used as a marker of lymphocytes T helper subsets cytokine secretion, was associated only with noncardiovascular mortality (hazard ratio 4.93; 95% confidence interval 1.03 to 23.65; P < 0.05).Conclusion: Beyond the strong prediction of cardiovascular mortality by IL-6, determination of cytokine ratios can be useful to identify hemodialysis patients with increased noncardiovascular mortality risk.