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Myeloperoxidase Levels and Its Product 3-Chlorotyrosine Predict Chronic Kidney Disease Severity and Associated Coronary Artery Disease.

Citation
Afshinnia, Farsad, et al. “Myeloperoxidase Levels and Its Product 3-Chlorotyrosine Predict Chronic Kidney Disease Severity and Associated Coronary Artery Disease”. 2017. American Journal of Nephrology, vol. 46, no. 1, 2017, pp. 73–81.
Center University of Michigan
Author Farsad Afshinnia, Lixia Zeng, Jaeman Byun, Crystal A Gadegbeku, Maria Chiara Magnone, Carl Whatling, Barbara Valastro, Matthias Kretzler, Subramaniam Pennathur, Michigan Kidney Translational Core CPROBE Investigator Group
Keywords biomarkers, cardiovascular, Chronic renal failure, inflammation, oxidative stress
Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSION: 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.

Year of Publication
2017
Journal
American journal of nephrology
Volume
46
Issue
1
Number of Pages
73-81
Date Published
12/2017
ISSN Number
1421-9670
DOI
10.1159/000477766
Alternate Journal
Am. J. Nephrol.
PMID
28668952
PMCID
PMC5560990
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