Renal Division, Department of internal Medicine, Peking University First Hospital, Beijing, 100034, China.
Institute of Nephrology, Peking University, Beijing, 100034, China.
J Cardiovasc Transl Res. 2019 Oct;12(5):496-505. doi: 10.1007/s12265-019-09885-2. Epub 2019 Apr 15.
The complement system plays an important role in cardiovascular disease in patients on hemodialysis. Vascular calcification is also one of the major causes of cardiovascular disease. We want to investigate the relationship between complement activation and vascular calcification in dialyzed patients. One hundred eight hemodialysis patients and 65 heathy controls were enrolled prospectively. Plasma C3a, C5a, mannose-binding lectin (MBL), and membrane attack complex (MAC or C5b-9) levels were detected using ELISA. Plasma C3c, fB, fH, C1q, and C4 levels were measured by immunity transmission turbidity. Abdominal aortic calcification (AAC) was measured by abdomen lateral plain radiograph, and the AAC score was calculated. We identified increased level of MBL and decreased level of C3c and complement factor B compared with normal control. However, C1q, complement factor H, and C4 levels remained at a similar level compared with individuals with normal renal function. The C3a and C5a levels increased, without change of MAC. Forty two of 108 HD patients had the AAC score. C3a levels were correlated with AAC score (r = 0.461, p = 0.002). The median C3a concentration was 238.72 (196.96, 323.41) ng/mL. When evaluated as AAC categories (≤ 4, > 5) with ordinal logistic regression, univariate analyses revealed that higher C3a levels were associated with severe AAC, while multivariate analyses adjusted for age, sex, and calcium level showed that higher C3a levels (OR, 6.28 (1.25-31.69); p = 0.03) were associated with severe AAC. The areas under the curve (AUC) for C3a to diagnose severe abdominal aortic calcification were 0.75(0.58-0.92, 0.01). The complement system was activated in patients on hemodialysis. Higher C3a levels are independently associated with severe AAC. Plasma C3a might have a diagnostic value for the severe AAC in HD patients.
补体系统在血液透析患者的心血管疾病中起着重要作用。血管钙化也是心血管疾病的主要原因之一。我们希望研究补体激活与透析患者血管钙化之间的关系。前瞻性纳入 108 例血液透析患者和 65 例健康对照者。采用 ELISA 法检测血浆 C3a、C5a、甘露糖结合凝集素(MBL)和膜攻击复合物(MAC 或 C5b-9)水平。采用免疫透射比浊法检测血浆 C3c、fB、fH、C1q 和 C4 水平。通过腹部侧位平片测量腹主动脉钙化(AAC),并计算 AAC 评分。与正常对照组相比,我们发现 MBL 水平升高,C3c 和补体因子 B 水平降低。然而,C1q、补体因子 H 和 C4 水平与肾功能正常者相比仍处于相似水平。C3a 和 C5a 水平升高,而 MAC 无变化。108 例血液透析患者中有 42 例有 AAC 评分。C3a 水平与 AAC 评分相关(r=0.461,p=0.002)。C3a 的中位数浓度为 238.72(196.96,323.41)ng/ml。当用有序逻辑回归进行 AAC 分类(≤4、>5)评估时,单变量分析显示,较高的 C3a 水平与严重 AAC 相关,而在调整年龄、性别和钙水平的多变量分析中,较高的 C3a 水平(OR,6.28(1.25-31.69);p=0.03)与严重 AAC 相关。C3a 诊断严重腹主动脉钙化的曲线下面积(AUC)为 0.75(0.58-0.92,0.01)。血液透析患者补体系统被激活。较高的 C3a 水平与严重 AAC 独立相关。血浆 C3a 对血液透析患者严重 AAC 可能具有诊断价值。