When should intravenous iron be administered to a chronic kidney disease patient on maintenance hemodialysis, based on ferritin, transferrin saturation, and erythropoiesis‑stimulating agent response?

When to Give IV Iron in CKD Hemodialysis Patients

Begin intravenous iron in hemodialysis patients when transferrin saturation (TSAT) is <20% and/or ferritin is <100 ng/mL. 1

Initiation Criteria

For hemodialysis patients, IV iron is the preferred route over oral iron because it provides superior efficacy, can be administered during dialysis sessions, and overcomes functional iron deficiency caused by elevated hepcidin levels. 1, 2

Laboratory Thresholds for Starting IV Iron

• TSAT <20% and/or ferritin <100 ng/mL: These are the primary triggers to initiate IV iron therapy in hemodialysis patients. 1
• Alternative threshold from KDIGO: TSAT ≤30% and ferritin ≤500 ng/mL may also be used when the goal is to increase hemoglobin without starting ESA therapy or to reduce ESA requirements. 3

The lower thresholds (TSAT <20%, ferritin <100 ng/mL) represent absolute iron deficiency, while the higher KDIGO thresholds capture functional iron deficiency where iron stores exist but are inadequate for optimal erythropoiesis. 4

Loading Phase Protocol

Administer 100–125 mg IV iron per hemodialysis session for 8–10 consecutive dialysis sessions (total cumulative dose 800–1,250 mg). 1

Specific Dosing by Preparation

• Iron sucrose: 100 mg per session for up to 10 doses. 5
• Ferric gluconate: 125 mg per session for 8 doses (replaces the older 10-dose regimen of 50 mg iron dextran). 1
• Low-molecular-weight iron dextran, ferric carboxymaltose, iron isomaltoside, and ferumoxytol: Permit higher single-dose infusions and faster administration than iron sucrose. 1

Critical timing: Check TSAT and ferritin 7 days after the final loading dose—earlier testing yields falsely elevated results. 1

Target Laboratory Parameters

Minimum Therapeutic Targets

Maintain TSAT ≥20% and ferritin ≥100 ng/mL to support adequate erythropoiesis and hemoglobin of 11–12 g/dL. 1

Optimal Targets for ESA Dose Reduction

Aim for TSAT 30–50% and ferritin 200–500 ng/mL to reduce ESA requirements by approximately 20–30% and improve cost-effectiveness. 1, 6

These higher targets reflect the reality that many hemodialysis patients have functional iron deficiency despite "normal" ferritin levels, because hepcidin blocks both intestinal iron absorption and reticuloendothelial iron recycling. 2, 4

Safety Thresholds: When to Stop IV Iron

Immediately discontinue IV iron if TSAT exceeds 50% or ferritin exceeds 800 ng/mL—further hemoglobin rise is unlikely beyond these levels, and risks of iron overload, infection, and mortality increase. 1, 7, 8

Resumption Protocol

• When parameters fall below the safety thresholds, resume iron at one-third to one-half of the previous maintenance dose. 1
• Recheck iron parameters 2–4 weeks after withholding. 7

Maintenance Phase Dosing

After achieving target hemoglobin and iron parameters, administer 25–125 mg IV iron weekly (or alternative schedules providing 250–1,000 mg within any 12-week period). 1, 7

Maintenance Regimen Options

• Standard: 125 mg ferric gluconate IV once weekly. 7
• Flexible schedules: Dosing can range from three times weekly to once every 2 weeks, depending on individual iron losses and erythropoietic demand. 1

Monitoring Requirements

Check TSAT, ferritin, and hemoglobin at least every 3 months during regular IV iron therapy. 3, 1, 7

Increased Monitoring Frequency

• When initiating or increasing ESA dose. 3
• When adjusting iron dose. 1
• After blood loss. 3
• Monthly monitoring if IV iron is not being given regularly. 1

Management of Inadequate Hemoglobin Response

If hemoglobin does not rise despite achieving TSAT ≥20% and ferritin ≥100 ng/mL, consider a second 10-dose course (total 1 g IV iron over 8–10 weeks) before labeling the patient iron-refractory. 1

Decision Algorithm After Second Course

• If hemoglobin improves with the second course at constant ESA dose—or remains stable while ESA is reduced—continue iron therapy. 1
• If TSAT or ferritin increase without corresponding hemoglobin rise, reduce the weekly iron dose to the lowest amount that maintains TSAT ≥20% and ferritin ≥100 ng/mL. 1

This approach recognizes that some patients have functional iron deficiency requiring higher iron stores, while others may have inflammation or other causes of ESA hyporesponsiveness. 4

Common Pitfalls and Caveats

Interpretation of Iron Markers

• Ferritin is an acute-phase reactant and may be elevated by inflammation independent of true iron stores; TSAT is generally more reliable for assessing iron availability for erythropoiesis. 4
• Patients can have TSAT ≥20% yet lack bone-marrow iron, supporting the use of higher TSAT targets (30–50%) for optimal therapy. 1

Oral Iron in Hemodialysis

Do not use oral iron in hemodialysis patients—it is inferior to IV iron due to poor intestinal absorption (caused by elevated hepcidin), greater iron losses during dialysis, and inability to meet the high iron turnover required for ESA-driven erythropoiesis. 1, 2, 6

Safety Monitoring

• Anaphylaxis risk is rare but slightly higher with larger carbohydrate-shell iron preparations (e.g., iron dextran). 1
• Test doses are no longer mandatory for low-molecular-weight iron dextran, though they may be considered in selected cases. 1
• Monitor patients for 60 minutes after the first infusion of any IV iron preparation, with resuscitative facilities and trained personnel available. 3

Avoiding Iron Overload

• Never continue iron when ferritin >800 ng/mL or TSAT >50%—this increases risk of iron overload, infection, and mortality without improving erythropoiesis. 1, 7, 8
• Do not measure iron studies immediately after dosing—wait at least 7 days after the final loading dose. 1, 7