Can intravenous (IV) iron supplementation increase the risk of urinary tract infections (UTI) in patients, particularly those with a history of UTI or underlying urological conditions?

Can IV Iron Increase Your Risk for a UTI?

Yes, intravenous iron administration is associated with an increased risk of infections, including urinary tract infections, and should be withheld during active infections. 1, 2

Evidence of Infection Risk

The most comprehensive and recent evidence comes from a 2021 systematic review and meta-analysis of 154 randomized clinical trials including 32,762 participants, which demonstrated that intravenous iron was associated with a statistically significant increased risk of infection overall (RR 1.16; 95% CI 1.03-1.29; moderate certainty evidence). 1 This translates to 16 additional people per 1,000 developing an infection when administered intravenous iron. 3

Specific Risk for Bacterial Infections

• For predominantly bacterial infections (including UTIs, sepsis, and skin/soft tissue infections), the risk appears more pronounced, with multiple analyses showing nominally elevated risk with increased iron stores. 1, 4
• A 2023 Mendelian randomization study specifically found that higher iron stores may increase odds of bacterial infections, including UTIs, even when accounting for confounding factors. 4

Biological Mechanism

The increased infection risk is mechanistically sound:

• Iron is essential for pathogen growth: Nearly all infectious microorganisms, including uropathogenic E. coli (UPEC), require iron for replication and survival. 1, 2
• Non-transferrin-bound iron: IV iron increases circulating non-transferrin-bound iron levels, which promotes pathogen growth and may be particularly important for gram-negative and siderophilic bacteria. 1
• Disruption of nutritional immunity: IV iron interferes with the body's natural process of withholding free iron from invading pathogens during inflammation. 1, 3
• UPEC-specific mechanisms: Uropathogenic E. coli can utilize ferric citrate uptake systems as a virulence factor, and this system is enriched in UPEC isolates compared to fecal strains. 5

Clinical Guidelines: When to Withhold IV Iron

All major guidelines uniformly recommend withholding IV iron during active infections:

• The Kidney Disease: Improving Global Outcomes (KDIGO) recommends withholding IV iron during active infections because these patients were systematically excluded from available randomized controlled trials. 1, 2
• The National Comprehensive Cancer Network explicitly states that patients with active infection should not receive IV iron therapy. 2
• The European Society for Medical Oncology reinforces that intravenous iron should not be given to patients with an active infection. 2
• The American College of Physicians recommends withholding all iron supplementation (oral and IV) until infection is cleared, and reassessing iron status after infection resolution (typically 7-14 days post-treatment). 6

Practical Clinical Algorithm

Before administering IV iron:

1. Screen for active infection by checking for fever, elevated inflammatory markers, and localized signs of infection (including UTI symptoms). 2
2. If active infection is present: Defer IV iron administration until infection is adequately controlled with antimicrobial therapy. 3, 6, 2
3. If no active infection: Proceed with appropriate IV iron formulation, but monitor for 30 minutes post-administration for hypersensitivity reactions. 2

For patients with history of recurrent UTIs:

• Consider the risk-benefit balance more carefully, as these patients may be at higher baseline risk. 6
• Ensure complete resolution of any UTI before initiating IV iron therapy. 3, 6
• In CKD patients on dialysis with UTI, temporarily withhold maintenance IV iron until infection clears. 6

Important Caveats

• Iron deficiency itself can impair immunity: While excess iron promotes infection, severe iron deficiency can also impair T-cell, B-cell, and neutrophil function. 1, 7 The key is avoiding iron supplementation during active infection, not avoiding correction of deficiency altogether.
• Timing matters: Once infection is cleared, iron supplementation should be resumed as indicated, as untreated iron deficiency has its own adverse consequences. 6
• Emergency situations: In life-threatening anemia requiring urgent correction during active infection, red blood cell transfusion is preferred over iron therapy. 3, 2
• Ferritin thresholds: Iron supplementation above ferritin >500 ng/mL is not recommended and potentially harmful. 6