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Plasma myeloperoxidase interactions with cadmium, lead, arsenic, and selenium and their impact on chronic kidney
Hsi-Hsien Chen1, Ya-Li Huang2, Chih-Yin Wu3
1Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
Abstract:
Myeloperoxidase (MPO) is an oxidative stress biomarker, with elevated MPO levels linked to chronic kidney disease (CKD) progression. Metal exposure is a risk factor for CKD, and is also correlated to MPO expression, with specific MPO genotypes linked to MPO expression. Therefore, we examined whether MPO plasma levels or MPO polymorphisms were linked to CKD, and explored whether these factors modified associations between CKD and metal concentrations. Accordingly, we recruited 395 age- and sex-matched controls and 215 patients with CKD (persistent estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 for a minimum of 12 weeks without hemodialysis). We identified no associations between several MPO genotypes and CKD. However, after multivariate adjustment, plasma MPO concentrations were positively correlated with CKD odds ratio (OR) = 5.87 (95 % confidence interval [CI]: 3.14-10.96). Significant additive interactions were observed between high plasma MPO concentrations and elevated blood cadmium (Cd) and lead (Pb) levels, and total urinary arsenic (As), or low plasma selenium (Se) concentrations, leading to increased ORs for CKD, with significant synergy indices recorded. High plasma MPO concentrations also showed multiplicative interactions with elevated blood Pb levels or low plasma Se concentrations, which increased the ORs for CKD (p-values = 0.005 and 0.009, respectively). Our study is the first to show a significant interaction between plasma MPO concentration and metals affecting the OR of CKD.
Insights
Elevated myeloperoxidase (MPO) plasma levels, but not MPO genotypes, are linked to chronic kidney disease (CKD). MPO interacts with metal exposures like cadmium, lead, arsenic, and selenium, increasing CKD risk.
Area of Science:
- Environmental Health
- Nephrology
- Biomarkers
Background:
- Myeloperoxidase (MPO) is an oxidative stress biomarker implicated in chronic kidney disease (CKD) progression.
- Metal exposure is a known risk factor for CKD and has been correlated with MPO expression.
- The interplay between MPO, genetic variations, and metal exposure in CKD pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the association between MPO plasma levels and polymorphisms with CKD.
- To explore whether MPO concentration or polymorphisms modify the relationship between metal exposure and CKD.
- To identify potential interactions between MPO and environmental metals in CKD development.
Main Methods:
- Recruitment of 215 CKD patients and 395 matched controls.
- Assessment of MPO plasma concentrations and MPO genotypes.
- Measurement of blood and urinary metal concentrations (cadmium, lead, arsenic, selenium).
- Multivariate regression analysis to determine odds ratios (OR) and interaction effects.
Main Results:
- No significant association was found between MPO genotypes and CKD.
- Elevated plasma MPO concentrations were positively correlated with CKD (OR = 5.87, 95% CI: 3.14-10.96) after adjustment.
- Significant additive and multiplicative interactions were observed between high plasma MPO and various metal exposures (Cd, Pb, As, Se) in increasing CKD risk.
Conclusions:
- Plasma MPO concentration is a significant risk factor for CKD, independent of MPO genotypes.
- MPO concentration interacts synergistically with environmental metals, amplifying CKD risk.
- This study highlights the crucial role of MPO in mediating the nephrotoxic effects of metal exposure.
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