Kidney Int. 2004 Jun;65(6):2279-89. Related Articles, Links

Oxidative stress and renal injury with intravenous iron in patients
with chronic kidney disease.

Agarwal R, Vasavada N, Sachs NG, Chase S.

Division of Nephrology, Department of Medicine, Indiana University
School of Medicine, and Richard L. Roudebush VA Medical Center,
Indianapolis, 46202, USA. ragarwal@iupui.edu

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.
CONCLUSION: 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.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15149341 [PubMed - indexed for MEDLINE]

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