In end‑stage renal disease (ESRD) patients with an active infection, should intravenous iron therapy be withheld?

Should Iron Be Held in ESRD Patients with Active Infection?

Yes, intravenous iron should be withheld during active infections in ESRD patients, as these patients were systematically excluded from randomized controlled trials and iron is essential for nearly all infectious microorganisms. 1

Guideline Consensus on Iron During Active Infection

The most recent KDIGO conference (2021) explicitly states that conference participants continue to recommend withholding i.v. iron during active infections because these patients were excluded from currently available RCTs. 1 This represents the highest-quality, most recent guideline recommendation available.

Earlier guidelines from 2008 similarly recommend that iron should be used with caution, if at all, in patients with active infection. 1 The 2008 guidelines also acknowledge this as a research gap, noting that RCTs are needed to determine whether iron supplementation should be continued in patients with potential infections. 1

Biological Rationale for Withholding Iron

The concern is well-founded based on microbiology:

• Iron is essential for nearly all infectious microorganisms, particularly gram-negative and other siderophilic bacteria 1
• Non-transferrin-bound iron may be particularly important as a risk factor for certain pathogens, especially gram-negative bacteria 1
• The theoretical risk is that providing iron during active infection could fuel bacterial growth and worsen outcomes 1

Distinction Between Infection and Inflammation

Critically, you should differentiate active infection from chronic inflammation:

• Intravenous iron therapy should be withheld during acute infection but not during inflammation 2
• Many ESRD patients have chronic inflammatory states (elevated CRP, ferritin as an acute-phase reactant) without active infection 1
• Chronic inflammation alone is not a contraindication to iron therapy 2

Practical Management Algorithm

During active infection:

1. Hold all scheduled intravenous iron administration until infection resolves 1, 2
2. Continue monitoring hemoglobin and iron parameters 3
3. Maintain erythropoiesis-stimulating agent (ESA) therapy if already prescribed 1
4. Resume iron therapy once infection has clinically resolved and inflammatory markers are improving 2

After infection resolution:

• Reassess iron status (transferrin saturation and ferritin) before resuming therapy 1, 3
• Resume iron supplementation to maintain TSAT ≥20% and ferritin ≥100 ng/mL 1, 3
• Monitor iron parameters every 1-3 months during maintenance therapy 1

Common Pitfalls to Avoid

Do not confuse elevated ferritin from inflammation with adequate iron stores - ferritin is an acute-phase reactant and may be falsely elevated during infection, making transferrin saturation a more reliable marker in this context. 1, 3

Do not assume oral iron is an adequate substitute during infection - while oral iron may theoretically be safer, hemodialysis patients almost universally require IV iron supplementation due to substantial blood losses that cannot be compensated by oral absorption. 3, 4

Do not permanently discontinue iron therapy based on a single infection - once the infection resolves, iron supplementation remains essential for anemia management in ESRD patients receiving ESA therapy. 2, 4

Evidence Limitations

The recommendation to withhold iron during infection is based primarily on exclusion of infected patients from clinical trials rather than direct evidence of harm. 1 No large randomized trials have specifically evaluated the safety of continuing versus withholding iron during active infections in ESRD patients. 1, 5 However, the precautionary principle applies given the biological plausibility of risk and lack of safety data. 1, 5