Treatment of Iron Deficiency Anemia in Non-Dialysis CKD Patients
For non-dialysis CKD patients with iron deficiency anemia, iron supplementation should be administered when hemoglobin is <110 g/L (11 g/dL) and either ferritin is <100 ng/mL or transferrin saturation (TSAT) is <20%, with the goal of maintaining ferritin ≥100 ng/mL and TSAT ≥20%. 1
Initial Assessment Requirements
Before initiating iron therapy, obtain the following laboratory tests 1:
- Complete blood count with hemoglobin, red cell indices, white blood cell count, differential, and platelet count
- Absolute reticulocyte count
- Serum ferritin level
- Transferrin saturation (TSAT)
- Serum vitamin B12 and folate levels
Important caveat: In non-dialysis CKD patients with iron deficiency (ferritin <100 ng/mL or TSAT <20%), carefully assess for gastrointestinal bleeding, as this is a common underlying cause that requires identification and treatment. 1
Iron Therapy Indications and Targets
When to Treat
Administer iron supplementation when ALL of the following criteria are met 1:
- Hemoglobin <110 g/L (11 g/dL)
- Ferritin <100 ng/mL OR TSAT <20%
Target Iron Parameters
Maintain the following iron indices 1, 2:
- Ferritin ≥100 ng/mL
- TSAT ≥20% (optimal range may be 30-50% for better ESA response)
Critical distinction: Treatment is NOT justified for patients with hemoglobin <110 g/L who lack classic iron deficiency (ferritin <25 ng/mL in males, <11 ng/mL in females), as there is insufficient evidence for benefit and potential for harm. 1
Route of Administration: IV vs Oral Iron
First-Line Approach
For non-dialysis CKD patients, either intravenous or oral iron is acceptable as initial therapy. 1, 3 The choice depends on:
- Severity of iron deficiency
- Availability of venous access
- Prior response to oral iron
- History of side effects with either route
- Patient compliance
- Cost considerations 1
IV Iron: Preferred in Specific Situations
Consider a trial of IV iron when 1:
- An increase in hemoglobin without starting ESA therapy is desired
- TSAT ≤30% and ferritin ≤500 ng/mL
- Patient has failed or is intolerant to oral iron
Evidence supporting IV iron superiority: In non-dialysis CKD patients, IV iron sucrose (200 mg weekly × 5 doses) resulted in 44.3% of patients achieving hemoglobin increase ≥1 g/dL compared to only 28% with oral ferrous sulfate (p=0.03). 4, 5 Additionally, IV iron patients with baseline ferritin <100 ng/mL had greater hemoglobin increases (1.4 g/dL) compared to oral iron (0.9 g/dL). 5
Oral Iron: Acceptable Alternative
Oral iron (ferrous sulfate 325 mg three times daily) can be used as initial therapy for 1-3 months 1, though it is less effective at replenishing iron stores. 5 Oral iron increases hemoglobin without substantially increasing ferritin, whereas IV iron increases both parameters. 5
Novel oral agents: Ferric citrate is FDA-approved for non-dialysis CKD patients with iron deficiency anemia and demonstrates improvements in hemoglobin and iron parameters with good tolerability. 4, 6
Dosing Regimens
IV Iron Sucrose (Venofer) - FDA Approved Regimens 4
Option 1: 200 mg IV over 2-5 minutes, given 5 times within 14 days (total 1000 mg)
Option 2: 500 mg IV infusion over 3.5-4 hours on Day 1 and Day 14 (total 1000 mg)
Oral Iron
Ferrous sulfate: 325 mg three times daily for 56 days 4
Special Considerations for Patients on ESA Therapy
For patients already receiving ESAs with suboptimal response (requiring high doses: ≥300 IU/kg/week epoetin or ≥1.5 mg/kg/week darbepoetin), consider iron supplementation even when ferritin is elevated (>800 ng/mL) if TSAT remains <25%. 1, 2 However, carefully weigh risks versus benefits of ongoing iron administration in this scenario. 1
Monitoring and Expected Response
Timeline for Response
- Hemoglobin increases typically occur within 2-4 weeks of IV iron initiation 1
- Ferritin and TSAT increase within 2 weeks and remain elevated at 4 weeks 4
Success Criteria
Clinical success is defined by 5:
- Hemoglobin increase ≥1 g/dL
- Achievement of hemoglobin >11 g/dL
- Combined endpoints of rises in hemoglobin/ferritin and hemoglobin/TSAT
Important finding: 55.3% of non-dialysis CKD patients with bone marrow-proven iron deficiency achieved target hemoglobin of 12 g/dL with IV iron alone, without requiring ESA therapy. 7
Safety Considerations
Balance potential benefits against risks 1:
- Benefits: Avoiding blood transfusions, minimizing ESA requirements, reducing anemia-related symptoms
- Risks: Anaphylactoid reactions (rare with modern preparations), unknown long-term risks
Practical safety measure: Ensure IV iron infusions occur in settings where monitoring for at least 30 minutes post-infusion is possible. 1
Common pitfall: Ferritin acts as an acute-phase reactant and may be falsely elevated in inflammatory states, making TSAT a more reliable indicator of true iron availability in these situations. 1, 2 Consider measuring C-reactive protein when ferritin is unexpectedly elevated. 1