What is the ideal ferritin level to start erythropoietin (EPO) in patients with Chronic Kidney Disease (CKD)?

Ideal Ferritin Level to Start EPO in CKD

Before initiating erythropoietin (EPO) therapy in CKD patients, ferritin should be >100 ng/mL and transferrin saturation (TSAT) should be >20%. 1

Iron Requirements Vary by CKD Population

The specific ferritin threshold differs based on dialysis status:

Non-Dialysis and Peritoneal Dialysis CKD Patients

• Ferritin >100 ng/mL and TSAT >20% are required before starting ESA therapy 1
• These patients can often maintain adequate iron stores with oral supplementation, though many will require intravenous iron 1

Hemodialysis CKD Patients

• Ferritin >200 ng/mL and TSAT >20% (or CHr >29 pg/cell) are the recommended targets before and during ESA therapy 1
• Higher thresholds are needed because hemodialysis patients have ongoing blood losses that exceed what oral iron can replace 1
• Studies demonstrate that maintaining ferritin at 200-400 ng/mL in hemodialysis patients results in 28% lower ESA dose requirements compared to maintaining ferritin at lower levels 1

Rationale for These Thresholds

Iron stores must be adequate before starting EPO because erythropoietin-stimulated erythropoiesis dramatically increases iron demand. 1 Without sufficient iron availability, patients will develop functional iron deficiency even if they have normal baseline iron stores. 1

• EPO therapy requires approximately 150 mg of iron for every 1 g/dL increase in hemoglobin 2
• Patients with TSAT <20% or ferritin <100 ng/mL frequently fail to respond adequately to ESA therapy 1
• Even patients with TSAT >20% may still have absent bone marrow iron stores, indicating functional iron deficiency 1, 3

Monitoring Strategy During ESA Initiation

Check TSAT and ferritin monthly during the initiation phase of EPO therapy until target hemoglobin (11-12 g/dL) is reached. 1

• After achieving stable hemoglobin, monitor iron parameters at least every 3 months 1
• The hemoglobin rise should be 1.0-2.0 g/dL per month and should not exceed 1 g/dL in any 2-week period 1

Common Pitfalls to Avoid

Do not start EPO without first ensuring adequate iron stores. 1 This is the most common cause of ESA hyporesponsiveness and leads to unnecessarily high EPO doses, increased costs, and potential adverse effects. 1

Ferritin can be falsely elevated in CKD due to inflammation (it is an acute-phase reactant), so consider measuring C-reactive protein if ferritin seems disproportionately high relative to TSAT. 4 Transferrin saturation is more reliable than ferritin alone for assessing iron availability because it is less affected by inflammation. 4

Upper safety limits exist: There is insufficient evidence to recommend IV iron if ferritin exceeds 500 ng/mL in non-dialysis patients 1 or 800 ng/mL in hemodialysis patients. 1, 4 Patients are unlikely to respond with further hemoglobin increases if TSAT reaches 50% or ferritin reaches 800 ng/mL. 1

Algorithm for Iron Repletion Before EPO

If iron parameters are inadequate before starting EPO:

1. For hemodialysis patients: Administer 1.0 g IV iron over 8-10 weeks (typically 100-125 mg weekly) 1
2. For non-dialysis/peritoneal dialysis patients: Trial oral iron (at least 200 mg elemental iron daily) first; if inadequate response after 3 months, switch to IV iron 1, 2
3. Reassess iron parameters after repletion and confirm ferritin and TSAT meet thresholds before initiating ESA 1