Parenteral iron nephrotoxicity: potential mechanisms and consequences

Area of Science:

• Nephrology
• Toxicology
• Biochemistry

Background:

• Parenteral iron is crucial for anemia in renal disease patients.
• Concerns about iron toxicity necessitate further toxicologic profiling.
• Understanding iron toxicity determinants is vital for patient safety.

Purpose of the Study:

• To evaluate the toxicologic profiles of different parenteral iron formulations.
• To identify potential determinants of iron-induced cytotoxicity in kidney cells.
• To assess both in vitro and in vivo iron toxicity in renal models.

Main Methods:

• Exposure of mouse proximal tubule segments and human kidney (HK-2) cells to iron sucrose, dextran, gluconate, and oligosaccharide.
• Assessment of cell injury via LDH release, ATP reduction, and cytochrome c efflux.
• In vivo toxicity evaluation through lipid peroxidation, ferritin, HO-1 mRNA expression, and electron microscopy.

Main Results:

• Iron preparations exhibited variable in vitro toxicity, with iron sucrose > iron gluconate > iron dextran = iron oligosaccharide.
• In vitro toxicity correlated with cellular iron uptake.
• In vivo findings showed increased renal oxidative stress markers and glomerular iron deposition with certain formulations (FeS, FeG).

Conclusions:

• Parenteral iron formulations possess variable cytotoxic potential, linked to cellular iron uptake.
• In vitro and in vivo data suggest potential for kidney injury at clinically relevant concentrations.
• Caution is advised when administering parenteral iron to patients with active renal disease.