Can intravenous (IV) iron cause red urine?

Intravenous Iron and Red Urine

Intravenous (IV) iron does not typically cause red urine, but discoloration of urine can occur in rare instances due to hemoglobinuria from hemolysis or iron excretion in specific clinical scenarios. 1

Potential Causes of Red/Discolored Urine with IV Iron

• IV iron preparations themselves do not directly cause red urine in normal circumstances 1
• Physiological iron losses through urine are minimal (approximately 0.1 mg/day), which is insufficient to cause visible discoloration 1
• Potential mechanisms for urine discoloration associated with IV iron therapy include:
  • Hemolysis: IV iron can rarely cause oxidative stress that may lead to hemolysis with subsequent hemoglobinuria appearing as red-colored urine 2, 3
  • Transferrin oversaturation: Some IV iron preparations, particularly when administered too rapidly, can cause "oversaturation" of transferrin, potentially leading to free iron that might be excreted 1

Risk Factors and Formulation Differences

• Different IV iron formulations have varying potential to cause adverse effects 1:
  • Iron gluconate > iron sucrose > iron dextran in terms of capacity to saturate transferrin directly 2
  • Newer formulations (ferric carboxymaltose, iron isomaltoside 1000, ferumoxytol) are more stable and have different pharmacokinetic profiles 1
• Risk factors for adverse effects include:
  • Rapid infusion rates 1
  • Higher single doses 1
  • Pre-existing kidney disease 2

Clinical Considerations

• IV iron can cause acute kidney injury and inflammation as demonstrated by increased urinary albumin and enzyme excretion 2
• Discolored urine following IV iron administration requires differentiation between:
  • Hemoglobinuria (from hemolysis) - positive for blood on dipstick but no RBCs on microscopy 3
  • Hematuria (blood in urine) - positive for blood on dipstick with RBCs on microscopy 3
  • Iron-containing pigments - may appear rusty or dark 4

Prevention and Management

• To minimize risk of adverse effects with IV iron administration 1:

  • Follow recommended infusion rates for specific iron preparations
  • Use appropriate dilution in saline as specified by manufacturer
  • Monitor for signs of hypersensitivity reactions during administration
  • Consider using newer, more stable IV iron formulations when available

• If red urine occurs after IV iron administration 3:

  • Perform urinalysis to differentiate between hematuria and hemoglobinuria
  • Assess for other signs of hemolysis (decreased hemoglobin, increased LDH, decreased haptoglobin)
  • Discontinue IV iron if hemolysis is suspected
  • Monitor kidney function

Special Considerations

• In dialysis patients, iron excretion patterns differ from those with normal kidney function 1
• A case report documented rusty-colored peritoneal dialysate fluid after IV iron dextran administration in a peritoneal dialysis patient, suggesting that iron can be excreted through peritoneal membrane 4
• IV iron staining of tissues can occur with extravasation (reported rate of 0.31% of infusions), which is a separate issue from urine discoloration 5

In conclusion, while IV iron itself does not typically cause red urine, clinicians should be aware that hemolysis-induced hemoglobinuria can rarely occur as a complication of IV iron therapy, potentially resulting in red-colored urine.