What is the recommended inpatient iron supplementation strategy for chronic hemodialysis patients, including preferred route, dosing thresholds, typical IV iron regimens, and monitoring parameters?

Intravenous Iron Supplementation for Hemodialysis Patients

For inpatient hemodialysis patients requiring iron supplementation, administer IV iron (not oral) using a maintenance regimen of 100-200 mg weekly or divided doses totaling 250-1000 mg over 12 weeks, targeting transferrin saturation ≥20% and ferritin ≥100 ng/mL. 1, 2

Preferred Route: Intravenous Over Oral

• IV iron is the preferred route for all hemodialysis patients because oral iron cannot maintain adequate iron stores in this population, is poorly absorbed, causes significant gastrointestinal side effects, and cannot overcome the functional iron deficiency common in dialysis patients 1
• IV iron demonstrates superior efficacy compared to oral iron, with significantly greater increases in ferritin (mean difference 243 μg/L) and transferrin saturation (mean difference 10.2%), while reducing erythropoiesis-stimulating agent (ESA) requirements by 20-30% 1
• The convenience of administering IV iron during dialysis sessions makes it the practical choice for this population 1

Iron Supplementation Thresholds

Initiate IV iron when:

• Transferrin saturation (TSAT) <20% OR ferritin <100 ng/mL 1
• Patient is receiving ESAs and requires optimization of iron stores 1

Withhold IV iron when:

• Ferritin >800 ng/mL OR TSAT >50%, as patients are unlikely to respond with further hemoglobin increases beyond these thresholds 1, 3
• Active infection is present 2

IV Iron Product Selection and Dosing Regimens

Available Formulations

Three main IV iron preparations are used, with newer formulations offering advantages over older ones 1, 2:

Iron Sucrose (Preferred for routine maintenance):

• No mandatory test dose required (though 25 mg test dose recommended for patients with previous sensitivities) 2
• Standard dose: 100-200 mg IV over 60 minutes 2, 3
• Can be administered directly into dialysis line 2-3 times weekly 3
• Individual doses above 300 mg not recommended 2

Ferric Gluconate (Ferrlecit):

• Test dose: 25 mg (strongly recommended for patients with previous sensitivities) 2
• Adult dose: 125 mg IV over 60 minutes 2
• Given weekly for 8 doses 2
• Individual doses above 125 mg not recommended 2

Iron Dextran:

• Mandatory test dose: 25 mg slow IV push, wait 1 hour before main dose 2
• If using iron dextran, choose low-molecular-weight formulation (INFeD) over high-molecular-weight (Dexferrum) due to fewer adverse events 2
• Dose: 100 mg IV over 5 minutes, repeated weekly for 10 doses 2
• Can give larger single doses (500-1000 mg) diluted in 250 mL normal saline over 1 hour 2

Recommended Dosing Strategies

Loading Phase (for iron-deficient patients):

• Administer 1000 mg total iron over 8-10 weeks 1
• For iron dextran: 100 mg weekly for 10 weeks 1, 2
• For ferric gluconate: 125 mg weekly for 8 weeks 1, 2
• For iron sucrose: 200 mg every 2-3 weeks 2

Maintenance Phase:

• Provide 250-1000 mg iron within each 12-week period 1, 2
• Frequency options: thrice weekly (with each dialysis), twice weekly, weekly, or every other week 1
• A high-dose proactive regimen (400 mg monthly unless ferritin >700 μg/L or TSAT ≥40%) is superior to reactive low-dose regimens, reducing cardiovascular events and mortality while lowering ESA requirements 4
• Need-based, continuous low-dose iron (10-60 mg, 1-3 times weekly based on ferritin and TSAT) achieves better hemoglobin response than intermittent pulse dosing 5

Monitoring Parameters

During initiation and dose escalation:

• Check TSAT and ferritin monthly in patients not receiving IV iron 1
• Check TSAT and ferritin at least every 3 months in patients receiving IV iron 1

During maintenance phase:

• Monitor TSAT and ferritin every 3 months 1, 2, 3
• Monitor hemoglobin at least every 3 months 6

Critical timing considerations:

• Do not measure TSAT or ferritin within 7 days after doses of 100-125 mg IV iron 1
• Do not measure within 14 days after single doses ≥1000 mg 1
• Optimal timing: measure 2-7 days after last dose for smaller doses, 7+ days for 100-125 mg doses 1

Safety and Administration Protocols

Pre-administration requirements:

• Ensure resuscitation facilities are available during administration 3
• Monitor vital signs during and after infusion 3
• Observe patient for at least 30 minutes post-infusion 1
• Administer only in hospital settings (per European guidelines) 1

Common adverse events:

• Hypotension, hypertension, nausea, vomiting, diarrhea, pain, fever, dyspnea, pruritus, headaches, dizziness 2
• Anaphylactoid reactions are rare but more common with iron dextran (especially high-molecular-weight) than non-dextran formulations 1
• Infusion-related adverse events occur in approximately 4.3% of patients 1

Important safety caveat:

• While high-dose IV iron improves outcomes in hemodialysis patients 4, doses exceeding 200 mg/month have been associated with increased cardiovascular disease, infections, and mortality in some observational studies 6
• The PIVOTAL trial demonstrated that proactive high-dose regimens (median 264 mg monthly) were actually superior to low-dose reactive regimens (median 145 mg monthly), with lower rates of cardiovascular events and death 4

Pediatric Dosing Adjustments

Iron dextran for pediatric hemodialysis patients (10-dose course):

• ≤10 kg: 25 mg per dose 1, 2
• 10-20 kg: 50 mg per dose 1, 2
• ≥20 kg: 100 mg per dose 1, 2

Iron sucrose for pediatric CKD patients:

• <10 kg: 25 mg per dose 3
• 10-20 kg: 50 mg per dose 3

• 20 kg: 100 mg per dose 3

Expected Response and Reassessment

• Expect hemoglobin increase of 0.9-1.0 g/dL within 4-8 weeks of therapy 1, 3
• If no hemoglobin increase after first 1000 mg course despite adequate TSAT and ferritin, administer a second course 1
• If still no response after second course but TSAT or ferritin increased, reduce to lowest weekly dose needed to maintain TSAT ≥20% and ferritin ≥100 ng/mL 1
• Serum iron <7.5 μmol/L predicts positive response to IV iron supplementation better than ferritin or TSAT alone 7