Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease.
BACKGROUND
Intravenous iron is widely prescribed in patients with chronic kidney disease (CKD) and can cause oxidative stress. The relationship of oxidative stress and renal injury in patients with CKD is unknown. Whether renal injury can occur at a time point when transferrin is incompletely saturated is also unclear.


METHODS
We conducted a randomized, open-label, parallel group trial to compare the oxidative stress induced by intravenous administration of 100 mg iron sucrose over 5 minutes and its protection with N-acetylcysteine (NAC) in 20 subjects with stage 3 or 4 CKD. Transferrin saturation was measured with urea polyacrylamide gel electrophoresis, oxidative stress by malondialdehyde (MDA) measurement by high-performance liquid chromatography, and renal injury by enzymuria and proteinuria. Reduced and oxidized glutathione and free radical scavengers as well as urinary monocyte chemoattractant protein-1 were also measured.


RESULTS
Parenteral iron increased plasma concentration and urinary excretion rate of MDA, a biomarker of lipid peroxidation, within 15 to 30 minutes of iron sucrose administration. This was accompanied by enzymuria and increase in proteinuria. In contrast, saturation of transferrin was not maximally seen until 3 hours after the end of infusion. Oxidative stress, enzymuria and proteinuria were transient and were completely resolved in 24 hours. NAC reduced acute generation of systemic oxidative stress but failed to abrogate proteinuria or enzymuria.


CONCLUSIONS
Intravenous iron produces oxidative stress that is associated with transient proteinuria and tubular damage. The rapid production of oxidative stress even when transferrin is not completely saturation suggests free iron independent mechanism(s) to be operative in producing oxidative stress and transient renal injury. Long-term implications of these findings need further study.
Agarwal
Rajiv
R
Division of Nephrology, Department of Medicine, Indiana University School of Medicine, and Richard L. Roudebush VA Medical Center, Indianapolis, 46202, USA. ragarwal@iupui.edu
Vasavada
Nina
N
Sachs
Nadine G
NG
Chase
Shawn
S
D000111:Acetylcysteine / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007501:Iron / Q000008:administration & dosage / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000293:injuries*; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects*; D014168:Transferrin / Q000378:metabolism
D016166:Free Radical Scavengers; D014168:Transferrin; D008315:Malondialdehyde; D007501:Iron; D000111:Acetylcysteine