Carbonyl stress induced by intravenous iron during haemodialysis.
BACKGROUND
Anaemic haemodialysis (HD) patients are treated with erythropoietin and intravenous iron for effective erythropoiesis. Since iron is a potent inducer and aggravator of pre-existing oxidative processes in HD patients, this study was aimed to evaluate the acute in vivo effect of two recommended iron doses on protein oxidation during the HD session.


METHODS
Iron gluconate was intravenously administered to HD patients in doses of 62.5 or 125 mg per session. A dialysis session without iron administration served as a control for each patient. Carbonylated fibrinogen and iron profile parameters were monitored before and after each session. Plasma carbonylated fibrinogen levels from healthy subjects and HD patients before dialysis were compared. Protein associated carbonyls were identified in plasma by derivatization with 2,4-dinitrophenylhydrazine followed by western analysis and were quantified by densitometry.


RESULTS
HD patients on maintenance iron showed elevated carbonylated fibrinogen compared with healthy subjects. During a HD session, carbonyls on fibrinogen further increased when 125 mg iron gluconate was administered, but no changes were detected with 62.5 mg iron gluconate or in the absence of iron. The changes in carbonylated fibrinogen during dialysis showed a significant linear correlation with the calculated values of transferrin saturation and free transferrin.


CONCLUSIONS
The significant acute increase in carbonylated fibrinogen with 125 mg iron gluconate suggests that this iron dose should be used with caution. As fibrinogen is highly susceptible to iron-induced oxidation in vivo, it may serve as a marker reflecting acute iron oxidative damage and as a tool in refinement of the existing clinical dose guidelines for intravenous iron therapy.
Michelis
Regina
R
Eliachar Research Laboratory, Western Galilee Hospital, Nahariya, Israel 22100.
Gery
Rafi
R
Sela
Shifra
S
Shurtz-Swirski
Revital
R
Grinberg
Natalie
N
Snitkovski
Tamara
T
Shasha
Shaul M
SM
Kristal
Batya
B
D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D016022:Case-Control Studies; D004921:Erythropoietin / Q000627:therapeutic use; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000009:adverse effects*; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects*; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism
D005290:Ferric Compounds; D011994:Recombinant Proteins; D014168:Transferrin; D004921:Erythropoietin; D005340:Fibrinogen; C035552:ferric gluconate