Myeloperoxidase Levels and Its Product 3-Chlorotyrosine Predict Chronic Kidney Disease Severity and Associated Coronary Artery Disease
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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.
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Acute kidney injury, glomerulonephritis, diabetic nephropathy, and bladder cancer have been associated with exposure to pathological chlorination stress.
“Among other pathologies, acute kidney injury, glomerulonephritis, diabetic nephropathy, and bladder cancer have been associated with exposure to pathological chlorination stress (110, 162–166).”
From Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer (2022) · cites this paper as [164]
Nephrotoxicity and urogenital tract dysfunction are established pathological outcomes of chlorination stress.
“Nephrotoxity and urogenital tract dysfunction are established pathological outcomes of chlorination stress.”
From Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer (2022) · cites this paper as [164]
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Protein damage and repair in aging: Mechanisms, homeostasis and disease
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- Authors
- Afshinnia, F., Zeng, L., Byun, J., Gadegbeku, C. A., Magnone, M. C., Whatling, C., Valastro, B., Kretzler, M., Pennathur, S., & Michigan Kidney Translational Core CPROBE Investigator Group
- Affiliations
- University of Michigan (US)
- AstraZeneca (Sweden) (SE)
- ORCID
- Venue
- American Journal of Nephrology
- Publisher
- S. Karger AG
- Published
- 2017
- Volume
- 46
- Issue
- 1
- Pages
- 73-81
- ISSN
- 0250-8095 (ISSN-L)
- 1421-9670
- PMC
- PMC5560990
- OpenAlex
- W2730977104
- Cited by
- 43
- References
- 46
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 6
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK082841, U24DK097153, P30DK081943, K08DK106523, P30DK020572, P30DK089503)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Keywords
- 3-chlorotyrosine, chronic kidney disease, coronary artery disease, CKD severity, end-stage renal disease, hypochlorous acid, oxidative stress, biomarkers, inflammation, CKD progression prediction, CKD-mineral and bone disorder
- MeSH terms
- Adult, Aged, Aged, 80 and over, Coronary Artery Disease, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Peroxidase, Risk Factors, Severity of Illness Index, Tyrosine, Biomarkers, Oxidative Stress, Renal Insufficiency, Chronic, Young Adult
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