Afshinnia Farsad, Zeng Lixia, Byun Jaeman, Gadegbeku Crystal A, Magnone Maria Chiara, Whatling Carl, Valastro Barbara, Kretzler Matthias, Pennathur Subramaniam
University of Michigan, Department of Internal Medicine-Nephrology, Ann Arbor, MI, USA.
Am J Nephrol. 2017;46(1):73-81. doi: 10.1159/000477766. Epub 2017 Jul 1.
The role of myeloperoxidase in chronic kidney disease (CKD) and its association with coronary artery disease (CAD) is controversial. In this study, we compared myeloperoxidase and protein-bound 3-chlorotyrosine (ClY) levels in subjects with varying degrees of CKD and tested their associations with CAD.
From Clinical Phenotyping Resource and Biobank Core, 111 patients were selected from CKD stages 1 to 5. Plasma myeloperoxidase level was measured using enzyme-linked-immunosorbent assay. Plasma protein-bound 3-ClY, a specific product of hypochlorous acid generated by myeloperoxidase was measured by liquid chromatography mass spectrometry.
We selected 29, 20, 24, 22, and 16 patients from stages 1 to 5 CKD, respectively. In a sex-adjusted general linear model, mean ± SD of myeloperoxidase levels decreased from 18.1 ± 12.3 pmol in stage 1 to 10.9 ± 4.7 pmol in stage 5 (p = 0.011). In patients with and without CAD, the levels were 19.1 ± 10.1 and 14.8 ± 8.7 pmol (p = 0.036). There was an increase in 3-ClY mean from 0.81 ± 0.36 mmol/mol-tyrosine in stage 1 to 1.42 ± 0.41 mmol/mol-tyrosine in stage 5 (p < 0.001). The mean 3-ClY levels in patients with and without CAD were 1.25 ± 0.44 and 1.04 ± 0.42 mmol/mol-tyrosine (p = 0.023), respectively. C-statistic of ClY when added to myeloperoxidase level to predict CKD stage 5 was 0.86, compared to 0.79 for the myeloperoxidase level alone (p = 0.0097).
The myeloperoxidase levels decrease from stages 1 to 5, whereas activity increases. In contrast, both myeloperoxidase and ClY levels rise in the presence of CAD at various stages of CKD. Measuring both plasma myeloperoxidase and 3-CLY levels provide added value to determine the burden of myeloperoxidase-mediated oxidative stress.
髓过氧化物酶在慢性肾脏病（CKD）中的作用及其与冠状动脉疾病（CAD）的关联存在争议。在本研究中，我们比较了不同程度CKD患者的髓过氧化物酶和蛋白结合3-氯酪氨酸（ClY）水平，并测试了它们与CAD的关联。
从临床表型资源库和生物样本库核心中，选取了111例1至5期CKD患者。采用酶联免疫吸附测定法测量血浆髓过氧化物酶水平。通过液相色谱质谱法测量血浆蛋白结合3-ClY，它是髓过氧化物酶产生的次氯酸的一种特定产物。
我们分别从1至5期CKD中选取了29例、20例、24例、22例和16例患者。在性别校正的一般线性模型中，髓过氧化物酶水平的均值±标准差从1期的18.1±12.3 pmol降至5期的10.9±4.7 pmol（p = 0.011）。在有和没有CAD的患者中，水平分别为19.1±10.1和14.8±8.7 pmol（p = 0.036）。3-ClY均值从1期的0.81±0.36 mmol/mol-酪氨酸增加到5期的1.42±0.41 mmol/mol-酪氨酸（p < 0.001）。有和没有CAD的患者的3-ClY平均水平分别为1.25±0.44和1.04±0.42 mmol/mol-酪氨酸（p = = 0.023）。当将ClY添加到髓过氧化物酶水平以预测CKD 5期时，C统计量为0.86，而单独的髓过氧化物酶水平为0.79（p = 0.0097）。
髓过氧化物酶水平从1期到5期降低，而活性增加。相比之下，在CKD的各个阶段，CAD存在时髓过氧化物酶和ClY水平均升高。同时测量血浆髓过氧化物酶和3-CLY水平为确定髓过氧化物酶介导的氧化应激负担提供了附加价值。
