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Impact of hemoglobin adducts of ethylene oxide on the prevalence and prognosis of chronic kidney disease in US adults: an analysis from NHANES 2013–2016

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Abstract

Animal experiments have shown that high exposure to ethylene oxide (EO) can cause multiple system damages including the renal system. Recent studies have reported associations between exposure to EO and cancer, dyslipidemia, diabetes, and cardiovascular disease. However, the impact of exposure to EO on the prevalence and prognosis of chronic kidney disease (CKD) in humans is scarcely investigated. The study was designed to investigate the associations between EO exposure and incidence and prognosis of CKD among 2900 US adults. Exposure to EO was measured by detecting the levels of hemoglobin adducts of EO (HbEO). The diagnosis of CKD was made according to an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) > 30 mg/g. Prognosis of CKD was assessed based on the evaluation system initiated by KDIGO that consists of eGFR and UACR. Survey-weighted generalized linear models and proportional odds models were constructed to assess the associations between HbEO and prevalence and prognosis of CKD, with odds ratios (ORs) and proportional odds ratios (PORs) and their 95% confidence intervals (CIs) reported, respectively. Restricted cubic spline (RCS) function was performed to depict the correlation between HbEO and CKD. The weighted median (interquartile range) of HbEO was 31.3 (23.1–60.3) pmol/g Hb. A total of 491 participants (16.9%) were diagnosed with CKD, and 153 participants (5.31%) were identified to be at high or very high risk. Referred to the first tertile of HbEO, the adjusted ORs (95% CIs) for CKD in the second and third tertile were 1.46 (0.85, 2.50) and 1.69 (1.00, 2.85), and the adjusted PORs (95% CIs) for prognosis of CKD in the second and third tertile were 1.37 (0.94, 1.99) and 1.58 (1.10, 2.26). When HbEO was analyzed as a continuous variable, the adjusted OR (95% CI) for CKD and POR (95% CI for prognosis of CKD were 1.24 (0.97, 1.58) and 1.22 (1.01, 1.47), respectively. RCS analysis revealed a non-linear positive correlation between HbEO and prevalence of CKD (P for nonlinearity < 0.05). Subgroup analysis indicated smoking status had a significant impact on this association, which remained significant among never smokers but lost significance among smokers. Among US adults, increased EO exposure was independently related to increased CKD prevalence and poor CKD outcomes, which was established in never smokers but not among ever smokers.

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Data availability

The NHANES data utilized in this paper is accessible to the public.

Abbreviations

BMI :

Body mass index

CKD :

Chronic kidney disease

CI :

Confidence interval

eGFR :

Estimated glomerular filtration rate

EO :

Ethylene oxide

HbEO :

Hemoglobin adduct N-(2-hydroxyethyl) valine

HPLC-MS/MS :

High-performance liquid chromatography coupled with tandem mass spectrometry

hs-CRP :

High-sensitivity C-reactive protein

KDIGO :

Kidney disease: improving global outcomes

MET :

Metabolic equivalent

MEC :

Mobile examination center

NCEH :

National Center for Environmental Health

NCHS :

National Center for Health Statistics

OR :

Odds ratio

POR :

Proportional odds ratio

RCS :

Restricted cubic spline

UACR :

Urine albumin to creatinine ratio

References

  • Armstrong T, Bull F (2006) Development of the World Health Organization Global Physical Activity Questionnaire (GPAQ). J Public Health 14:66–70

    Article  Google Scholar 

  • Bogen KT, Sheehan PJ, Valdez-Flores C, Li AA (2019) Reevaluation of historical exposures to ethylene oxide among US sterilization workers in the National Institute of Occupational Safety and Health (NIOSH) study cohort. Int J Environ Res Public Health 16:1738

    Article  CAS  Google Scholar 

  • Boogaard PJ, Rocchi PS, van Sittert NJ (1999) Biomonitoring of exposure to ethylene oxide and propylene oxide by determination of hemoglobin adducts: correlations between airborne exposure and adduct levels. Int Arch Occup Environ Health 72:142–150

    Article  CAS  Google Scholar 

  • CDC (2023) Centers for disease control and prevention: the National Health and Nutritional Examination Survey (NHANES) analytic and reporting guidelines. CDC, Atlanta https://wwwn.cdc.gov/nchs/nhanes/analyticguidelines.aspx

    Google Scholar 

  • Chavers BM, Simonson J, Michael AF (1984) A solid-phase fluorescent immunoassay for the measurement of human urinary albumin. Kidney Int 25:576–578

    Article  CAS  Google Scholar 

  • Filser JG, Klein D (2018) A physiologically based toxicokinetic model for inhaled ethylene and ethylene oxide in mouse, rat, and human. Toxicol Lett 286:54–79

    Article  CAS  Google Scholar 

  • Fletcher BR, Damery S, Aiyegbusi OL et al (2022) Symptom burden and health-related quality of life in chronic kidney disease: a global systematic review and meta-analysis. PLoS Med 19:e1003954

    Article  Google Scholar 

  • GBD (2019) Diseases and Injuries Collaborators (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 396:1204–1222

    Google Scholar 

  • Guo J, Wan Z, Cui G, Pan A, Liu G (2021) Association of exposure to ethylene oxide with risk of diabetes mellitus: results from NHANES 2013-2016. Environ Sci Pollut Res Int 28:68551–68559

    Article  CAS  Google Scholar 

  • Hollingsworth RL, Rowe VK, Oyen F (1956) Toxicity of ethylene oxide determined on experimental animals. AMA Arch Ind Health 13:217–227

  • Hu W, Li G, He J, Zhao H, Zhang H, Lu H, Liu J, Huang F (2023) Association of exposure to multiple serum metals with the risk of chronic kidney disease in the elderly: a population-based case-control study. Environ Sci Pollut Res Int 30:17245–17256

    Article  CAS  Google Scholar 

  • Kirman CR, Hays SM (2017) Derivation of endogenous equivalent values to support risk assessment and risk management decisions for an endogenous carcinogen: ethylene oxide. Regul Toxicol Pharmacol 91:165–172

    Article  CAS  Google Scholar 

  • Kirman CR, Li AA, Sheehan PJ, Bus JS, Lewis RC, Hays SM (2021) Ethylene oxide review: characterization of total exposure via endogenous and exogenous pathways and their implications to risk assessment and risk management. J Toxicol Environ Health B Crit Rev 24:1–29

    Article  CAS  Google Scholar 

  • Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) (2009). A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604-612

  • Levin A, Stevens PE, Bilous RW, Coresh J, De Francisco ALM, De Jong PE, Griffith KE, Hemmelgarn BR, Iseki K, Lamb EJ, Levey AS, Riella MC, Shlipak MG, Wang H, White CT, Winearls CG (2013) Kidney disease: improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150

    Google Scholar 

  • Li Z, Shi P, Chen Z, Zhang W, Lin S, Zheng T, Li M, Fan L (2023) The association between ethylene oxide exposure and asthma risk: a population-based study. Environ Sci Pollut Res Int 30:24154–24167

    Article  CAS  Google Scholar 

  • Liu W, Cao S, Ma J, Shi D, Yu L, Ye Z, Yang M, Wang B, Chen W (2023) Exposures to volatile organic compounds, serum vitamin D, and kidney function: association and interaction assessment in the US adult population. Environ Sci Pollut Res Int 30:7605–7616

    Article  CAS  Google Scholar 

  • Lumley T, Scott AJ (2015) AIC and BIC for modelling with complex survey data. J Surv Stat Methodol 3:1–18

    Article  Google Scholar 

  • Lynch HN, Kozal JS, Russell AJ, Thompson WJ, Divis HR, Freid RD, Calabrese EJ, Mundt KA (2022) Systematic review of the scientific evidence on ethylene oxide as a human carcinogen. Chem Biol Interact 364:110031

    Article  CAS  Google Scholar 

  • Matsushita K, Ballew SH, Wang AY, Kalyesubula R, Schaeffner E, Agarwal R (2022) Epidemiology and risk of cardiovascular disease in populations with chronic kidney disease. Nat Rev Nephrol 18:696–707

    Article  Google Scholar 

  • Mihai S, Codrici E, Popescu ID, Enciu AM, Albulescu L, Necula LG, Mambet C, Anton G, Tanase C (2018) Inflammation-related mechanisms in chronic kidney disease prediction, progression, and outcome. J Immunol Res 2018:2180373

    Article  Google Scholar 

  • Rao JNK, Scott AJ (1984) On chi-squared tests for multiway contingency tables with cell proportions estimated from survey data. Ann Statist 12:46–60

    Article  Google Scholar 

  • Schettgen T, Broding HC, Angerer J, Drexler H (2002) Hemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile and acrylamide-biomarkers in occupational and environmental medicine. Toxicol Lett 134:65–70

    Article  CAS  Google Scholar 

  • Stumbo P (2008) Considerations for selecting a dietary assessment system. J Food Compos Anal 21:S13–S19

    Article  Google Scholar 

  • Szwiec E, Friedman L, Buchanan S (2020) Levels of ethylene oxide biomarker in an exposed residential community. Int J Environ Res Public Health 17:8646

    Article  CAS  Google Scholar 

  • Toxicological Profile for Ethylene Oxide (2022). Agency for toxic substances and disease registry (US).

    Google Scholar 

  • US Department of Health and Human Services and US Department of Agriculture (2015) 2015-2020 dietary guidelines for Americans, 8th edn https://health.gov/our-work/food-nutrition/previous-dietary-guidelines/2015

    Google Scholar 

  • Webster AC, Nagler EV, Morton RL, Masson P (2017) Chronic kidney disease. Lancet 389:1238–1252

    Article  Google Scholar 

  • Wu N, Cao W, Wang Y, Liu X (2022) Association between blood ethylene oxide levels and the prevalence of hypertension. Environ Sci Pollut Res Int 29:76937–76943

    Article  CAS  Google Scholar 

  • Zhang J, Wang X, Ma Z, Dang Y, Yang Y, Cao S, Ouyang C, Shi X, Pan J, Hu X (2023) Associations of urinary and blood cadmium concentrations with all-cause mortality in US adults with chronic kidney disease: a prospective cohort study. Environ Sci Pollut Res Int 30:61659–61671

    Article  CAS  Google Scholar 

  • Zeng G, Zhang Q, Wang X, Wu KH (2021) Association between blood ethylene oxide levels and the risk of cardiovascular diseases in the general population. Environ Sci Pollut Res Int 28:64921–64928

    Article  CAS  Google Scholar 

  • Zhu X, Kong X, Chen M, Shi S, Cheang I, Zhu Q, Lu X, Yue X, Tang Y, Liao S, Zhou Y, Zhang H, Yao W, Li X (2022) Blood ethylene oxide, systemic inflammation, and serum lipid profiles: results from NHANES 2013-2016. Chemosphere 299:134336

    Article  CAS  Google Scholar 

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Acknowledgements

We sincerely thank all staff for their industrious contributions and all participants in the NHANES program. We would like to express our gratitude to Prof. Zhang Jing from Shanghai Tongren Hospital for his invaluable contribution to our analysis of the NHANES database. The nhanesR package and webpage that he developed have greatly facilitated our work with the database.

Funding

This study received financial support from the Capital’s Funds for Research and Application of Clinical Diagnosis and Treatment Technology with reference number Z191100006619121.

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Authors and Affiliations

  1. Emergency Center, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing, People’s Republic of China

    Shuang Wu, Yan-min Yang, Jun Zhu, Lu-lu Wang, Wei Xu, Si-qi Lyu, Juan Wang, Xing-hui Shao & Han Zhang

  2. National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Shuang Wu, Yan-min Yang, Jun Zhu, Lu-lu Wang, Wei Xu, Si-qi Lyu, Juan Wang, Xing-hui Shao & Han Zhang

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  1. Shuang Wu
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Contributions

YMY and JZ designed and supervised the study. SW carried out the statistical analysis and drafted the paper. SW, LLW, WX, SQL, JW, HZ, and XHS were responsible for data extraction and cleaning. YMY and JZ revised the manuscript and approved the final version for publication. All authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Yan-min Yang.

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Ethics and informed consent

The Ethics Committee of the National Center for Health Statistics gave approval to the NHANES protocols, and participants were informed of the study and signed informed consent form.

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The authors declare no competing interests.

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Responsible Editor: Lotfi Aleya

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Wu, S., Yang, Ym., Zhu, J. et al. Impact of hemoglobin adducts of ethylene oxide on the prevalence and prognosis of chronic kidney disease in US adults: an analysis from NHANES 2013–2016. Environ Sci Pollut Res 31, 2802–2812 (2024). https://doi.org/10.1007/s11356-023-30712-4

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