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Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease.

Abstract

BACKGROUND

Increased common carotid artery intima-media thickness (CCA-IMT) is a marker of early atherosclerosis. Low-grade inflammation is associated with the pathogenesis of atherosclerosis. Low-grade inflammation and increased CCA-IMT are observed in end-stage renal disease (ESRD). Oxidative stress is involved in uremia-related inflammation. Advanced oxidation protein products (AOPP) are markers of oxidant-mediated protein damage in ESRD. Intravenous iron given to patients on hemodialysis (HD) might induce oxidative stress. We investigated the relationships between AOPP, iron therapy, and CCA-IMT in stable HD patients.

METHODS AND RESULTS

Plasma AOPP and blood chemistry, including iron status, were analyzed in a cohort of 79 ESRD patients on HD. Measurements of CCA-IMT and CCA diameter, as assessed by B-mode ultrasonography, were obtained in 60 patients. AOPP levels were elevated in ESRD patients, and in univariate (r=0.42, P<0.0001) and multivariate analyses (r=0.38, P<0.001), they correlated with serum ferritin and with the intravenous iron dose received during the 12 months preceding the study (ferritin, P<0001; AOPP, P<0.01). Univariate and multivariate analyses identified the AOPP concentration as being significantly associated with CCA-IMT (P=0.0197) and CCA wall-to-lumen ratio (r=0.560, P<0.0001). Independently of AOPP concentration, cumulative iron dose was positively related to CCA-IMT (P=0.015) in patients <60 years.

CONCLUSION

In ESRD patients, CCA-IMT and CCA wall-to-lumen ratio were associated with plasma AOPP, serum ferritin, and the annual intravenous iron dose administered. These findings support the concept of a role of oxidative stress in the early atherosclerosis of ESRD patients, which may be increased by the usually recommended doses of intravenous iron.

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  • Authors+Show Affiliations

    ,

    INSERM U507 and Service de Néphrologie, Hôpital Necker, Paris, France.

    , , , , , ,

    Source

    Circulation 106:17 2002 Oct 22 pg 2212-7

    MeSH

    Biomarkers
    Carotid Artery Diseases
    Carotid Artery, Common
    Cohort Studies
    Dose-Response Relationship, Drug
    Female
    Ferritins
    Humans
    Iron
    Kidney Failure, Chronic
    Male
    Middle Aged
    Multivariate Analysis
    Oxidative Stress
    Proteins
    Renal Dialysis
    Risk Factors
    Tunica Intima
    Tunica Media
    Ultrasonography

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    12390950

    Citation

    Drüeke, Tilman, et al. "Iron Therapy, Advanced Oxidation Protein Products, and Carotid Artery Intima-media Thickness in End-stage Renal Disease." Circulation, vol. 106, no. 17, 2002, pp. 2212-7.
    Drüeke T, Witko-Sarsat V, Massy Z, et al. Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease. Circulation. 2002;106(17):2212-7.
    Drüeke, T., Witko-Sarsat, V., Massy, Z., Descamps-Latscha, B., Guerin, A. P., Marchais, S. J., ... London, G. M. (2002). Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease. Circulation, 106(17), pp. 2212-7.
    Drüeke T, et al. Iron Therapy, Advanced Oxidation Protein Products, and Carotid Artery Intima-media Thickness in End-stage Renal Disease. Circulation. 2002 Oct 22;106(17):2212-7. PubMed PMID: 12390950.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease. AU - Drüeke,Tilman, AU - Witko-Sarsat,Véronique, AU - Massy,Ziad, AU - Descamps-Latscha,Béatrice, AU - Guerin,Alain P, AU - Marchais,Sylvain J, AU - Gausson,Valérie, AU - London,Gérard M, PY - 2002/10/23/pubmed PY - 2002/11/26/medline PY - 2002/10/23/entrez SP - 2212 EP - 7 JF - Circulation JO - Circulation VL - 106 IS - 17 N2 - BACKGROUND: Increased common carotid artery intima-media thickness (CCA-IMT) is a marker of early atherosclerosis. Low-grade inflammation is associated with the pathogenesis of atherosclerosis. Low-grade inflammation and increased CCA-IMT are observed in end-stage renal disease (ESRD). Oxidative stress is involved in uremia-related inflammation. Advanced oxidation protein products (AOPP) are markers of oxidant-mediated protein damage in ESRD. Intravenous iron given to patients on hemodialysis (HD) might induce oxidative stress. We investigated the relationships between AOPP, iron therapy, and CCA-IMT in stable HD patients. METHODS AND RESULTS: Plasma AOPP and blood chemistry, including iron status, were analyzed in a cohort of 79 ESRD patients on HD. Measurements of CCA-IMT and CCA diameter, as assessed by B-mode ultrasonography, were obtained in 60 patients. AOPP levels were elevated in ESRD patients, and in univariate (r=0.42, P<0.0001) and multivariate analyses (r=0.38, P<0.001), they correlated with serum ferritin and with the intravenous iron dose received during the 12 months preceding the study (ferritin, P<0001; AOPP, P<0.01). Univariate and multivariate analyses identified the AOPP concentration as being significantly associated with CCA-IMT (P=0.0197) and CCA wall-to-lumen ratio (r=0.560, P<0.0001). Independently of AOPP concentration, cumulative iron dose was positively related to CCA-IMT (P=0.015) in patients <60 years. CONCLUSION: In ESRD patients, CCA-IMT and CCA wall-to-lumen ratio were associated with plasma AOPP, serum ferritin, and the annual intravenous iron dose administered. These findings support the concept of a role of oxidative stress in the early atherosclerosis of ESRD patients, which may be increased by the usually recommended doses of intravenous iron. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/12390950/Iron_therapy_advanced_oxidation_protein_products_and_carotid_artery_intima_media_thickness_in_end_stage_renal_disease_ L2 - http://www.ahajournals.org/doi/full/10.1161/01.cir.0000035250.66458.67?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -