NDT Advance Access originally published online on February 27, 2006
Nephrology Dialysis Transplantation 2006 21(7):2035-2036; doi:10.1093/ndt/gfl050
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Antioxidant treatment in dialysis patients— importance of ferritin
Email: alpersoy{at}uludag.edu.trSir,
Cardiovascular disease remains one of the leading causes of mortality in haemodialysis (HD) patients. Abnormal oxidative stress and impaired antioxidant defence may contribute to accelerated atherogenesis associated with uraemia. I read with interest the article by Fumeron et al. [1], reporting that short-term oral vitamin C supplementation did not modify well-defined oxidative/antioxidative stress and inflammation markers in HD patients. As stated, they did not evaluate the effect of long-term intravenous vitamin C supplementation with lower or higher doses on oxidative stress, nor the efficacy of co-administration of vitamin E.
Iron is a powerful oxidizing substance. Ferritin may have other functions in addition to its well-described role in storing intracellular iron. Elevated ferritin levels are associated with an increased risk of atherosclerotic coronary artery disease and myocardial infarction. Recent proteomics and molecular biology studies have shown that ferritin levels in arteries are increased in diseased tissues [2]. Ferritin may be unregulated under particular physiological conditions and may act as a pro-oxidant. In the mammalian cell, iron stored in ferritin can participate in initiating lipid peroxidation [3].
High levels of serum ferritin may indicate iron overload. However, in many patients results may be elevated due to inflammation, even if iron stores are not increased. Limited evidence shows that elevated iron stores and high-dose intravenous iron therapy may increase morbidity and mortality in HD patients [4], and exacerbate increased oxidative stress in uraemic patients [5].
The upper limit of serum ferritin that has a potential for oxidative tissue damage related to increased iron storage or to intravenous iron treatment itself is unclear [6]. Reddi et al. [7] did not find a difference either in antioxidant enzymes, antioxidants or lipid peroxidation between dialysis patients with normal (<325 ng/ml) or higher than normal (>325 ng/ml) serum ferritin levels. On the contrary, in another study [8], malondialdehyde levels of dialysis patients with the highest ferritin levels (657–1251 µg/l) were significantly greater than those of the other two groups with lower ferritin levels (296–556 µg/l and 559–804 µg/l). In addition, this study showed that elevated serum ferritin levels may affect the levels of these lipophilic antioxidants. However, there is no study comparing malnutrition, inflammation, oxidative stress markers and atherosclerosis status in HD patients with high or low ferritin levels in detail.
Perhaps, Fumeron et al. [1] could divide the subjects into two groups with low and high ferritin levels by determining a cutoff ferritin value. Whether baseline oxidative/antioxidative stress parameters differ in these groups and change with oral 250 mg vitamin C supplementation in the vitamin C group could be evaluated. Thus, this study may provide an approach to the strategies of antioxidant treatment in the dialysis population.
Conflict of interest statement. None declared.
Uludag University Medical Faculty Nephrology Bursa Turkey
References
- Fumeron C, Nguyen-Khoa T, Saltiel C et al. Effects of oral vitamin C supplementation on oxidative stress and inflammation status in haemodialysis patients. Nephrol Dial Transplant 2005; 20: 1874–1879
[Abstract/Free Full Text] - You SA, Wang Q. Ferritin in atherosclerosis. Clin Chim Acta 2005; 357: 1–16[CrossRef][ISI][Medline]
- Puntarulo S. Iron, oxidative stress and human health. Mol Aspects Med 2005; 26: 299–312[Medline]
- Kletzmayr J, Horl WH. Iron overload and cardiovascular complications in dialysis patients. Nephrol Dial Transplant 2002; 17 [Suppl 2]: 25–29[Abstract]
- Lim PS, Wei YH, Yu YL, Kho B. Enhanced oxidative stress in haemodialysis patients receiving intravenous iron therapy. Nephrol Dial Transplant 1999; 14: 2680–2687
[Abstract/Free Full Text] - Fishbane S, Kalantar-Zadeh K, Nissenson AR. Serum ferritin in chronic kidney disease: reconsidering the upper limit for iron treatment. Semin Dial 2004; 17: 336–341[CrossRef][ISI][Medline]
- Reddi AS, Bollineni JS, Baskin S, Nimmagadda VR, Baker H. Serum ferritin and oxidative stress in patients undergoing hemodialysis. Nephron 2000; 86: 202–203[Medline]
- Lim PS, Chan EC, Lu TC et al. Lipophilic antioxidants and iron status in ESRD patients on hemodialysis. Nephron 2000; 86: 428–435[CrossRef][Medline]
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