High iron storage levels are associated with increased DNA oxidative injury in patients on regular hemodialysis.
BACKGROUND
Accumulating evidence suggests that oxidative stress is enhanced in patients on regular hemodialysis (HD). Iron supplementation is essential for the treatment of renal anemia, but there is a possibility that it could enhance oxidative stress by inducing the Fenton reaction. Here, we report our investigation of the relation between iron storage and DNA oxidative injury in HD patients.


METHODS
The study subjects were 48 patients on regular HD (age, 62.7 +/- 12.1 years; HD duration, 67.2 +/- 62.5 months; non-diabetic/diabetic; 22:26). Patients who were positive for hepatitis C virus antibody (HCV Ab), or hepatitis B surface antigen (HBsAg), and those with inflammatory or malignant diseases were excluded. The serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) level, a marker of DNA oxidative injury, was measured before the first HD session of the week in all patients, and factors associated with high serum 8-OHdG were investigated. In 9 patients with a serum ferritin level of more than 1000 ng/ml at study entry, serum 8-OHdG levels were followed up for 6 months in the absence of iron supplementation.


RESULTS
Multivariate analysis showed that the serum ferritin level was a significant and independent determinant of serum 8-OHdG, and serum ferritin correlated significantly with the total dose of iron supplementation during the 6-month period of the study. In the nine patients, without iron supplementation, serum 8-OHdG levels, as well as serum ferritin, decreased significantly during follow-up.


CONCLUSIONS
Our results suggest that increased iron storage may induce DNA oxidative injury in patients on regular HD, and that the serum ferritin level is a surrogate marker for this pathological condition.
Department of Kidney and Hypertension, Tokyo Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo 105-8461, Japan. washu@jikei.ac.jp
Kazunobu
K
Yoshimura
Hirofumi
H
Nakano
Keitaro
K
Yokoyama
Masaaki
M
Nakayama
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005293:Ferritins / Q000097:blood*; D005500:Follow-Up Studies; D006801:Humans; D007501:Iron / Q000009:adverse effects* / Q000493:pharmacokinetics; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D014168:Transferrin / Q000378:metabolism
D014168:Transferrin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005293:Ferritins; D007501:Iron; D003849:Deoxyguanosine