NDT Advance Access originally published online on January 29, 2007
Nephrology Dialysis Transplantation 2007 22(5):1407-1412; doi:10.1093/ndt/gfl789
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Effect of repeated intravenous iron administration in haemodialysis patients on serum 8-hydroxy-2'-deoxyguanosine levels
1Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan, 2Reseach Division of Dialysis and Chronic Kidney Disease, Tohoku University Graduate School of Medicine, Sendai, Japan and 3Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Correspondence and offprint requests to: Yukio Maruyama MD, Division of Kidney and Hypertension, The Jikei University School of Medicine, 3-19-18 Nishi-shinbashi, Minato-ku, Tokyo, 105-8471, Japan. Email: maruyama{at}td5.so-net.ne.jp
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Background. Iron supplementation is a mainstay for management of renal anaemia in patients receiving haemodialysis (HD). Although it is well known that a single intravenous iron (IVIR) administration transiently enhances oxidative stress in HD patients, the consequence of repeated IVIR administration is still unknown. This study aims to clarify the time course of changes in serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative injury, during a period of repeated IVIR administration in HD patients.
Methods. Twenty-seven patients (62 ± 14 years and 23 males) on long-term HD participated in this study. All patients had been on HD more than 6 months and none had received a blood transfusion or iron therapy in previous 6 months. The patients were divided into three groups according to the baseline haematocrit (Ht) and serum ferritin (FTN) levels as a marker of body iron stores: IVIR group (Ht < 30% and FTN < 100 ng/ml; n = 7); High FTN group (Ht
30% and FTN
100 ng/ml; n = 11); and low FTN group (Ht
30% and FTN < 100 ng/ml; n = 9). The IVIR group patients received 40 mg of ferric saccharate i.v. after each HD session until Ht increased by 5%. Serum 8-OHdG and other parameters were prospectively monitored for 10 weeks.
Results. At baseline, the serum ferritin level was independently associated with 8-OHdG in a multiple regression model (total adjusted R2 = 0.47, P < 0.01). All patients in the IVIR group achieved the target Ht level during the study. IVIR administration resulted in significant increases in 8-OHdG levels (0.22 ± 0.070.50 ± 0.16 ng/ml: baseline to 10 week) as compared with both the high FTN group (0.52 ± 0.200.58 ± 0.28 ng/ml) and the low FTN group (0.39 ± 0.110.36 ± 0.11 ng/ml) (ANOVA for repeated measures P < 0.01). Additionally, serum 8-OHdG and serum ferritin changed in the same manner.
Conclusions. Repeated IVIR administration for HD patients was associated with signs of increased oxidative DNA injury, as reflected by increased serum levels of 8-OHdG. As these changes were accompanied by increased serum ferritin levels, excess body iron stores might play an important role in oxidative stress.
Keywords: anaemia; haemodialysis; 8-hydroxy-2'-deoxyguanosine (8-OHdG); intravenous iron administration; oxidative stress
Received for publication: 20. 5.06
Accepted in revised form: 5.12.06
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