What are the guidelines for iron supplementation in patients with End-Stage Renal Disease (ESRD)?

Iron Supplementation in ESRD Patients

Most hemodialysis patients with ESRD require regular intravenous iron supplementation to maintain adequate iron stores and optimize erythropoiesis, with target transferrin saturation ≥20% and serum ferritin ≥100 ng/mL. 1

Why IV Iron is Essential in Hemodialysis

Oral iron is inadequate for hemodialysis patients due to:

• Substantial ongoing blood losses from dialyzer procedures (approximately 400 mg iron lost every 3 months) 1
• Blood remaining in dialysis tubing and dialyzer 1
• Frequent blood sampling 1
• Gastrointestinal bleeding 1
• Poor intestinal absorption that cannot compensate for these losses 1, 2
• Increased iron demand from erythropoiesis-stimulating agent (ESA) therapy (approximately 600 mg additional iron needed to raise hematocrit from 25% to 35%) 1

Target Iron Parameters

Maintain these minimum thresholds:

• Transferrin saturation (TSAT) ≥20% 1, 3
• Serum ferritin ≥100 ng/mL 1, 3

Higher targets optimize ESA response:

• TSAT 30-50% and ferritin >200 ng/mL reduce ESA requirements by up to 40% 1, 4
• Patients with TSAT 20-30% may still have functional iron deficiency despite adequate ferritin 4

Initial IV Iron Dosing Protocol

For iron-deficient patients (TSAT <20% and/or ferritin <100 ng/mL):

• Administer 100-125 mg IV iron at each hemodialysis session for 8-10 consecutive doses 1, 3
• This provides the 1,000 mg typically needed during initial ESA therapy 1
• Use iron sucrose 100 mg undiluted over 2-5 minutes or diluted in 100 mL normal saline over 15 minutes 5
• Alternatively, use ferric gluconate 125 mg diluted in 100 mL normal saline over 1 hour 6

Maintenance IV Iron Dosing

Once target iron parameters are achieved:

• Administer 25-125 mg IV iron weekly to maintain hemoglobin targets and prevent iron depletion 1, 3
• Most patients require 400-500 mg supplemental iron every 3 months for maintenance 1
• Adjust the weekly dose based on TSAT and ferritin levels measured at least every 3 months 1, 3

Upper Safety Limits and When to Withhold Iron

Withhold IV iron when:

• TSAT >50% and/or ferritin >800 ng/mL 1, 3
• Hold for up to 3 months, then recheck iron parameters before resuming 1
• When resuming, reduce the weekly dose by one-third to one-half 1

Important context on upper limits:

• Ferritin levels of 300-800 ng/mL are common in dialysis patients without evidence of adverse iron-mediated effects 1, 7
• The exact level at which iron overload occurs remains unknown 1
• TSAT >80% is associated with transfusional hemosiderosis, but no known risk exists with TSAT ≤50% 1

Monitoring Strategy

Check TSAT and ferritin at least every 3 months during maintenance therapy 1, 3

Interpret results in context:

• Ferritin is an acute-phase reactant and may be falsely elevated during inflammation or infection 1, 7
• Consider checking C-reactive protein if inflammation is suspected 7
• TSAT is more reliable than ferritin for assessing iron availability in the presence of inflammation 7
• Functional iron deficiency can occur when TSAT <20% despite ferritin >100 ng/mL, especially in patients on ESAs 1, 8

Special Considerations for Functional Iron Deficiency

When TSAT <20% but ferritin is adequate (100-500 ng/mL):

• This represents functional iron deficiency where iron stores exist but are not available for erythropoiesis 4, 9
• Additional IV iron should be given if hemoglobin <11 g/dL or ESA doses are higher than anticipated 1
• Continue iron supplementation as long as it does not chronically maintain TSAT >50% or ferritin >800 ng/mL 1

Administration Safety

Test dose requirements:

• Iron dextran: Give one-time test dose of 25 mg IV in adults before initiating therapy 1
• Iron gluconate: Give one-time test dose of 25 mg IV diluted in 50 mL normal saline over 60 minutes 1, 6
• Monitor for immediate allergic reactions (occur in <1% of administrations) 1

Monitoring during administration:

• Observe patients for at least 30 minutes after infusion and until clinically stable 6
• Have personnel and therapies immediately available to treat anaphylaxis 6
• Monitor for hypotension, which can occur during or after administration 6

Common Pitfalls to Avoid

• Do not rely on oral iron alone in hemodialysis patients—it is inadequate to maintain iron stores during ESA therapy 1
• Do not withhold iron based solely on elevated ferritin if TSAT is low and inflammation is present—this may represent functional iron deficiency 1, 7, 8
• Do not continue iron indefinitely without monitoring—check TSAT and ferritin every 3 months to prevent iron overload 1, 3
• Do not administer iron during acute infection, though inflammation alone is not a contraindication 10
• Do not target normal ferritin ranges (as in hemochromatosis management)—ESRD patients require higher ferritin levels (>200 ng/mL) to support erythropoiesis 7