What are the guidelines for iron supplementation in patients with Chronic Kidney Disease (CKD)?

Iron Supplementation in Chronic Kidney Disease

Primary Recommendation

Iron should be administered to CKD patients with hemoglobin < 110 g/L when ferritin is < 100 ng/mL or transferrin saturation (TSAT) is < 20%, with intravenous iron being the preferred route for hemodialysis patients and either IV or oral iron acceptable for non-dialysis CKD patients. 1

Assessment of Iron Status

Before initiating iron therapy, measure both ferritin and TSAT to determine the type and severity of iron deficiency 2, 3:

• Absolute iron deficiency: TSAT ≤ 20% AND ferritin < 100 ng/mL (non-dialysis/peritoneal dialysis) or < 200 ng/mL (hemodialysis) 4
• Functional iron deficiency: TSAT ≤ 20% with ferritin > 100 ng/mL, indicating adequate stores but insufficient availability for erythropoiesis 4

Important caveat: Do not treat patients without classic iron deficiency (ferritin < 25 ng/mL in males, < 11 ng/mL in females) if hemoglobin is < 110 g/L, as efficacy and clinical benefit remain unproven 1

Route of Administration by CKD Stage

Hemodialysis Patients (CKD Stage 5D)

Intravenous iron is the preferred and necessary route 1, 4:

• Initial dosing: 100-125 mg IV per hemodialysis session for 8-10 consecutive sessions 1
• Maintenance: 25-125 mg IV weekly once target iron indices achieved 1
• Rationale: Oral iron is poorly absorbed and ineffective at maintaining adequate iron stores in hemodialysis patients due to ongoing blood losses and increased iron demands from ESA therapy 1, 2, 5

Non-Dialysis CKD (Stages 3-5) and Peritoneal Dialysis

Either IV or oral iron is acceptable, though IV iron is preferred when feasible 6, 4:

• Oral iron trial: 200 mg elemental iron daily for adults (2-3 mg/kg for pediatrics) for 1-3 months 1, 6
• IV iron alternative: 500-1,000 mg iron dextran as single infusion (after 25 mg test dose) or 100-125 mg weekly for 8-10 weeks 1, 6
• Switch to IV if: Inadequate response to oral iron after 1-3 months, gastrointestinal intolerance, or need for rapid iron repletion 6, 7

Target Iron Indices

Maintain the following targets during treatment 1:

• Ferritin: ≥ 100 ng/mL (≥ 200 ng/mL for hemodialysis patients on ESAs) 1
• TSAT: ≥ 20% (target 20-30% for optimal erythropoiesis) 1

Upper safety limits 1, 2:

• Stop iron when: Ferritin > 500-800 ng/mL OR TSAT > 50% 1, 2, 6
• Rationale: Patients are unlikely to respond with further hemoglobin increases beyond these thresholds, and risks of iron overload increase 1

Special Consideration: High Ferritin with Low TSAT

In patients with ferritin 500-1,200 ng/mL but TSAT < 25% who are below target hemoglobin or requiring high ESA doses (≥ 300 IU/kg/week epoetin or ≥ 1.5 mg/kg/week darbepoetin), consider administering IV iron to increase hemoglobin 1:

• This represents functional iron deficiency despite elevated ferritin 1
• Carefully assess risk-benefit balance, as long-term safety of high-dose IV iron at these ferritin levels remains uncertain 1, 8
• The DRIVE study demonstrated hemoglobin increases with IV iron in this population, but mortality and cardiovascular outcomes were not assessed 1

Monitoring Schedule

During initiation and dose adjustment 1, 2:

• Check TSAT and ferritin monthly in patients not receiving IV iron
• Check TSAT and ferritin every 3 months in patients receiving IV iron
• Monitor hemoglobin weekly until stable, then monthly 3

Once treatment is established 1, 2, 6:

• Check TSAT and ferritin at least every 3 months
• Check hemoglobin at least every 3 months

Timing considerations for accurate measurement 1:

• Wait 7 days after doses of 100-125 mg IV iron before checking iron parameters
• Wait 14 days after single doses ≥ 1,000 mg IV iron
• Doses ≤ 100 mg weekly do not require interruption for accurate measurement

Common Pitfalls and How to Avoid Them

Pitfall 1: Relying on oral iron alone in hemodialysis patients 1, 2

• Solution: Recognize that oral iron is inadequate for most hemodialysis patients due to poor absorption and ongoing losses; transition to IV iron early

Pitfall 2: Continuing iron supplementation beyond safe upper limits 1, 8

• Solution: Strictly adhere to ferritin < 500-800 ng/mL and TSAT < 50% thresholds; withhold iron for up to 3 months when exceeded 1

Pitfall 3: Treating with iron when hemoglobin is already at target 1

• Solution: Iron therapy decisions must integrate hemoglobin level, ESA dose, and patient status—not just iron indices alone 1

Pitfall 4: Failing to evaluate for other causes of anemia 3

• Solution: Before initiating or escalating iron therapy, exclude vitamin deficiency, bleeding, inflammatory conditions, and other reversible causes 3

Pitfall 5: Using benzyl alcohol-containing formulations in vulnerable populations 3

• Solution: Use only single-dose, benzyl alcohol-free vials in pregnant women, lactating women, neonates, and infants 3

Safety Considerations

Hypersensitivity reactions 9:

• Observe patients for at least 30 minutes after IV iron administration
• Ensure personnel and therapies for treating serious reactions are immediately available
• Consider test doses for dextran-containing preparations 5

Hypotension risk 9:

• Monitor for signs and symptoms during and after each IV iron administration
• More common with rapid infusion rates

Iron overload 9:

• Regularly monitor hematologic responses
• Do not administer to patients with existing iron overload
• Long-term safety of high-dose IV iron with ferritin > 500 ng/mL remains incompletely established 8