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


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.


CONCLUSIONS
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.
Drüeke
Tilman
T
INSERM U507 and Service de Néphrologie, Hôpital Necker, Paris, France.
Witko-Sarsat
Véronique
V
Massy
Ziad
Z
Descamps-Latscha
Béatrice
B
Guerin
Alain P
AP
Marchais
Sylvain J
SJ
Gausson
Valérie
V
London
Gérard M
GM
D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000209:etiology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007501:Iron / Q000009:adverse effects / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018384:Oxidative Stress; D011506:Proteins / Q000032:analysis; D006435:Renal Dialysis; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
D015415:Biomarkers; D011506:Proteins; D005293:Ferritins; D007501:Iron