What is the recommended intravenous iron supplementation regimen for adult dialysis patients with anemia of chronic kidney disease, including dosing, target transferrin saturation and ferritin levels, and monitoring?

Iron Supplementation for Dialysis Patients

Direct Recommendation

For adult hemodialysis patients with anemia of chronic kidney disease, administer 100-125 mg of intravenous iron per dialysis session for 8-10 consecutive doses as initial therapy, targeting TSAT ≥20% and ferritin ≥100 ng/mL, with mandatory cessation when TSAT exceeds 50% or ferritin exceeds 800 ng/mL. 1, 2

Initial Loading Phase Regimen

Dosing Protocol:

• Administer 100 mg iron sucrose per hemodialysis session, up to three times weekly 1
• Complete 8-10 total doses for severe iron deficiency 1, 3
• Iron gluconate can be substituted at 125 mg per dose for 8 doses (versus 10 doses of 50 mg iron dextran) 4
• Newer formulations (low-molecular-weight iron dextran, ferric carboxymaltose, iron isomaltoside 1000, ferumoxytol) allow higher single doses and more rapid administration than iron sucrose 4

Initiation Criteria:

• Begin IV iron when TSAT <20% and/or ferritin <100 ng/mL 4, 2
• IV iron is preferred over oral iron for hemodialysis patients due to superior efficacy, convenience during dialysis sessions, and ability to overcome functional iron deficiency 4, 5

Target Laboratory Parameters

Minimum Thresholds:

• TSAT ≥20% 4, 1, 2
• Ferritin ≥100 ng/mL 4, 1, 2
• Hemoglobin 11-12 g/dL 4, 2

Optimal Targets for ESA Dose Reduction:

• TSAT 30-50% 4, 3
• Ferritin 200-500 ng/mL 4, 2
• Higher targets reduce ESA requirements by 20-30% and improve cost-effectiveness 4

Critical Safety Thresholds

Mandatory Withholding Criteria:

• Immediately stop IV iron if TSAT >50% or ferritin >800 ng/mL 4, 1, 2
• Recheck parameters in 2-4 weeks after withholding 1
• Patients are unlikely to respond with further hemoglobin increases beyond these thresholds 4

Resumption Protocol:

• When parameters fall below safety thresholds, resume at one-third to one-half the previous maintenance dose 1

Monitoring Requirements

During Loading Phase:

• Check TSAT and ferritin 7 days after the final loading dose—not sooner, as earlier measurements yield falsely elevated results 1
• Monitor iron parameters at least every 3 months during regular IV iron administration 4, 1
• Check monthly if not receiving IV iron regularly 4

During Maintenance Phase:

• Monitor TSAT, ferritin, and hemoglobin every 3 months 2, 3
• More frequent monitoring may be needed when adjusting therapy 4

Maintenance Therapy

Dosing Range:

• 25-125 mg weekly, administered anywhere from three times weekly to once every 2 weeks 1
• Total iron within any 12-week period: 250-1,000 mg 1
• Goal: maintain TSAT ≥20% and ferritin ≥100 ng/mL while avoiding chronic elevation above safety thresholds 1, 2

Individualized Approach:

• Need-based, continuous low-dose iron (10-60 mg, 1-3 times weekly) based on monthly ferritin and TSAT values may achieve better hemoglobin response with lower total iron doses 6

Management of Inadequate Response

If No Hemoglobin Increase Despite Adequate Iron Parameters:

• Consider a second 10-dose course (1.0 g IV iron over 8-10 weeks) before concluding the patient is iron-refractory 4, 1
• If hemoglobin increases with either course at constant ESA dose, or remains stable at decreased ESA dose, continue iron therapy 4
• If TSAT or ferritin increases without hemoglobin response, reduce to lowest weekly dose needed to maintain TSAT ≥20% and ferritin ≥100 ng/mL 4

Important Clinical Caveats

Interpretation Challenges:

• Ferritin is an acute-phase reactant and may be elevated due to inflammation independent of iron stores in dialysis patients 2, 7
• TSAT may be more reliable than ferritin for assessing iron availability for erythropoiesis 2
• Patients with TSAT ≥20% may still have absent bone marrow iron, supporting higher target thresholds 4

Safety Considerations:

• Test doses may be advisable for low-molecular-weight iron dextran but are no longer mandatory 4
• Risk of anaphylaxis remains rare but is slightly higher with larger carbohydrate shell preparations 4
• IV iron increases risk of hypotension but reduces gastrointestinal adverse events compared to oral iron 5
• Concerns exist regarding iron overload, infection risk, and mortality with aggressive iron supplementation, particularly when ferritin exceeds 800 ng/mL 4, 8

Route Selection:

• IV iron is definitively superior to oral iron in hemodialysis patients, producing greater increases in ferritin (mean difference 243 μg/L) and TSAT (mean difference 10.2%), with moderate hemoglobin increase (0.9 g/dL) 4
• Elevated hepcidin levels in dialysis patients impair intestinal iron absorption, making oral iron ineffective 9