What is the initial treatment for iron deficiency anemia in patients with end-stage renal disease (ESRD)?

Treatment of Iron Deficiency Anemia in End-Stage Renal Disease

Intravenous iron is the initial and preferred treatment for iron deficiency anemia in patients with end-stage renal disease (ESRD), particularly those on hemodialysis. 1

Route of Administration: IV Iron is Standard of Care

For hemodialysis patients with ESRD, intravenous iron should be used rather than oral iron. 1 The NKF-K/DOQI guidelines explicitly state that "oral iron is not indicated for the CKD" patients on hemodialysis, and that "most hemodialysis patients will require intravenous iron on a regular basis." 1 This recommendation is based on the superior efficacy of IV iron in this population, where gastrointestinal absorption is impaired and ongoing blood losses are substantial. 1

• Oral iron may be considered first only in non-dialysis CKD patients, but even then, IV iron should be used if oral iron is not tolerated or fails to meet iron status targets. 1
• For hemodialysis patients specifically, IV iron is the standard approach because of poor oral absorption, ongoing blood losses from dialysis procedures, and the need to support erythropoiesis-stimulating agent (ESA) therapy. 1

Initial Dosing Protocol for Hemodialysis Patients

When transferrin saturation (TSAT) is <20% and/or serum ferritin is <100 ng/mL, administer 100-125 mg of IV iron at every hemodialysis session for 8-10 consecutive doses. 1 This loading phase rapidly replenishes iron stores and supports erythropoiesis.

• If iron parameters remain inadequate (TSAT <20% and/or ferritin <100 ng/mL) after the initial course, repeat another 8-10 week course of 100-125 mg weekly. 1
• Once adequate iron status is achieved (TSAT ≥20% and ferritin ≥100 ng/mL), transition to maintenance dosing of 25-125 mg IV weekly. 1

Choice of IV Iron Formulation

Select IV iron formulations that can replace iron deficits with 1-2 infusions when possible, as these are more convenient and improve adherence. 1 Available FDA-approved options include:

• Iron sucrose (Venofer): Maximum 200 mg per dose, 10-minute infusion, indicated for IDA in CKD patients. 2
• Ferric gluconate (Ferrlecit): Indicated for iron deficiency anemia in hemodialysis patients receiving ESA therapy. 3
• Ferric carboxymaltose (Injectafer): Can deliver up to 1,000 mg in a single 15-minute infusion. 4

Iron dextran preparations carry higher risk of anaphylactoid reactions (0.6-0.7%) compared to non-dextran formulations, and serious reactions including fatalities have been reported. 1 Non-dextran preparations (iron sucrose, ferric gluconate) are generally preferred for safety. 1

Monitoring Iron Status

Monitor TSAT and serum ferritin every 1-3 months during active treatment. 1 More frequent monitoring is required when:

• Initiating or increasing ESA dose 1
• After blood loss 1
• Monitoring response after IV iron course 1

Target iron parameters for hemodialysis patients:

• TSAT >20% 1
• Ferritin >100 ng/mL 1
• Most patients achieve target hemoglobin (11-12 g/dL) with TSAT >50% and ferritin >800 ng/mL 1

Safety Considerations and Upper Limits

Withhold IV iron when TSAT >50% and/or ferritin >800 ng/mL for up to 3 months, then reassess iron parameters before resuming at a reduced dose (one-third to one-half of previous dose). 1 This prevents iron overload while maintaining adequate stores.

Critical safety precautions:

• Monitor patients for 60 minutes after initial dose of iron dextran, and after initial dose of non-dextran iron formulations. 1
• Ensure resuscitation facilities and trained personnel are immediately available. 1
• All IV iron formulations carry risk of hypersensitivity reactions, though true anaphylaxis is rare; most reactions are complement activation-related pseudo-allergy. 1
• Use IV iron with caution during active infection, though it should not be withheld during chronic inflammation. 1, 5

Integration with ESA Therapy

Address iron deficiency before initiating or escalating ESA therapy. 1 Iron deficiency is the most common cause of ESA hyporesponsiveness in ESRD patients. 6, 5

• For hemodialysis patients on ESA therapy, maintain TSAT >20% and ferritin >100 ng/mL with ongoing IV iron supplementation. 1
• Iron therapy improves hemoglobin response, reduces ESA dose requirements, and has non-erythropoietic benefits including improved physical performance. 7

Common Pitfalls to Avoid

Do not rely on oral iron in hemodialysis patients – it is ineffective due to poor absorption and cannot keep pace with ongoing losses. 1

Do not continue aggressive IV iron dosing when ferritin exceeds 800 ng/mL – recent evidence suggests high cumulative IV iron doses may lead to hepatic iron overload and potentially increase cardiovascular events, though this remains controversial. 1, 8

Do not withhold iron during chronic inflammation – functional iron deficiency commonly occurs in ESRD patients with elevated inflammatory markers, and IV iron can still be beneficial. 5