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on October 7, 2002

Circulation. 2002
Published online before print October 7, 2002, doi: 10.1161/01.CIR.0000035250.66458.67
A more recent version of this article appeared on October 22, 2002
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Submitted on June 13, 2002
Revised on August 9, 2002
Accepted on August 9, 2002

Iron Therapy, Advanced Oxidation Protein Products, and Carotid Artery Intima-Media Thickness in End-Stage Renal Disease

Tilman Drüeke MD, Véronique Witko-Sarsat PhD, Ziad Massy MD, Béatrice Descamps-Latscha MD, PhD, Alain P. Guerin MD, Sylvain J. Marchais MD, Valérie Gausson MS, and Gérard M. London MD*

From INSERM U507 and Service de Néphrologie, Hôpital Necker, Paris (T.D., V.W.-S., Z.M., B.D.-L., V.G.), and Service d'Hémodialyse, Hôpital F.H. Manhès, Fleury-Mérogis (A.P.G., S.J.M., G.L.), France.

* To whom correspondence should be addressed. E-mail: glondon{at}club-internet.fr.

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.


Key words: renal dialysis • oxidative stress • atherosclerosis • iron




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