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in vivo glomerular iron deposition/injury may result
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Kidney Int. 2004 Jul;66(1):144-56. Related Articles, Links
Parenteral iron nephrotoxicity: Potential mechanisms and consequences.
Zager RA, Johnson AC, Hanson SY.
Department of Medicine, university of Washington, Seattle, Washington.
Parenteral iron nephrotoxicity: Potential mechanisms and consequences.
Background. Parenteral iron administration is a mainstay of anemia management
in renal disease patients. However, concerns of potential iron toxicity
persist. Thus, this study was conducted to more fully gauge iron toxicologic
profiles and potential determinants thereof. Methods. Isolated mouse proximal
tubule segments (PTS) or cultured proximal tubular [human kidney (HK-2)] cells
were exposed to four representative iron preparations [iron sucrose (FeS), iron
dextran (FeD), iron gluconate (FeG), or iron oligosaccharide (FeOS)] over a
broad dosage range (0, 30 to 1000 microg iron/mL). Cell injury was assessed by
lactate deyhdrogenase (LDH) release, adenosine triphosphate (ATP) reductions,
cell cytochrome c efflux, and/or electron microscopy. In vivo toxicity (after 2
mg intravenous iron injections) was assessed by plasma/renal/cardiac lipid
peroxidation [malondialdehyde (MDA)], renal ferritin (protein)/heme oxygenase-1
(HO-1) (mRNA) expression, electron microscopy, or postiron injection PTS
susceptibility to attack. Results. In each test, iron evoked in vitro toxicity,
but up to 30x differences in severity (e.g., ATP declines) were observed (FeS >
FeG > FeD = FeOS). The in vitro differences paralleled degrees of cell (HK-2)
iron uptake. In vivo correlates of iron toxicity included variable increases in
renal MDA, ferritin, and HO-1 mRNA levels. Again, these changes appeared to
parallel in vivo (glomerular) iron uptake (seen with FeS and FeG, but not with
FeD or FeOS). Iron also effected in vivo alterations in proximal tubule cell
homeostasis, as reflected by the "downstream" emergence of tubule resistance to
in vitro oxidant attack. Conclusion. Parenteral iron formulations have potent,
but highly variable, cytotoxic potentials which appear to parallel degrees of
cell iron uptake (FeS > FeG >> FeD or FeOS). That in vitro injury can be
expressed at clinically relevant iron concentrations, and that in vivo
glomerular iron deposition/injury may result, suggest caution is warranted if
these agents are to be administered to patients with active renal disease.
PMID: 15200421 [PubMed - in process]
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