How to manage anemia in a patient with Chronic Kidney Disease (CKD) and elevated ferritin levels?

Managing Anemia in CKD with Elevated Ferritin

In CKD patients with elevated ferritin, continue iron supplementation if transferrin saturation (TSAT) is ≤30% and ferritin is ≤500 ng/mL, as elevated ferritin often reflects inflammation rather than iron overload, and functional iron deficiency remains common even with high ferritin levels. 1, 2

Understanding Elevated Ferritin in CKD

Ferritin is fundamentally misleading in CKD patients because it functions as an acute-phase reactant that rises with inflammation, independent of actual iron stores. 2, 3

• Ferritin levels up to 500-700 ng/mL may still represent functional iron deficiency when inflammation is present, which is extremely common in CKD patients. 2
• Inflammation drives ferritin elevation even when tissue iron stores are normal or low, particularly in hemodialysis patients. 2
• TSAT is more reliable than ferritin for assessing iron availability because it is less affected by inflammation. 2

Iron Therapy Decision Algorithm Based on Current Guidelines

For CKD Patients NOT on ESA Therapy:

Consider a trial of IV iron (or oral iron in non-dialysis CKD) when: 1

• TSAT ≤30% AND ferritin ≤500 ng/mL
• Goal is to increase hemoglobin without starting ESA therapy
• Active infection has been excluded

For CKD Patients ON ESA Therapy:

Administer IV iron when: 1, 4

• TSAT <20% OR ferritin <100 ng/mL (non-dialysis/peritoneal dialysis)
• TSAT <20% OR ferritin <200 ng/mL (hemodialysis patients) 5
• Goal is to increase hemoglobin or decrease ESA dose requirements

The majority of CKD patients will require supplemental iron during ESA therapy, regardless of ferritin levels. 4

Upper Safety Thresholds

Withhold IV iron when: 1

• TSAT >50% AND/OR ferritin >800 ng/mL
• Withhold for up to 3 months, then re-measure iron parameters
• When resuming, reduce IV iron dose by one-third to one-half

Critical distinction: Ferritin levels between 300-800 ng/mL have been common in dialysis patients without evidence of adverse iron-mediated effects. 1, 2 Recent guidelines suggest maintaining ferritin <500 ng/mL in non-dialysis CKD, but hemodialysis patients may safely maintain higher levels. 2

Distinguishing Functional Iron Deficiency from Inflammatory Block

When ferritin is elevated but TSAT is low, this suggests inflammatory iron block rather than adequate iron stores. 2

Therapeutic trial approach: 2

• Administer weekly IV iron (50-125 mg) for 8-10 doses
• If no erythropoietic response occurs, inflammatory block is likely
• Withhold further iron until inflammation resolves
• Measure C-reactive protein to assess inflammatory contribution 2

Practical Dosing for Hemodialysis Patients

For iron deficiency (TSAT <20% and/or ferritin <100 ng/mL): 1

• Administer 100-125 mg IV iron at every hemodialysis session for 8-10 doses
• If parameters remain low, repeat another course

For maintenance (once TSAT ≥20% and ferritin ≥100 ng/mL): 1

• Administer 25-125 mg IV iron once weekly
• Most patients require ongoing IV iron to maintain target hemoglobin 1

Monitoring Requirements

Monitor iron status (TSAT and ferritin) at least every 3 months during ESA therapy. 1

Monitor more frequently when: 1

• Initiating or increasing ESA dose
• Blood loss occurs
• Monitoring response after IV iron course
• Hemoglobin is unstable

Critical Pitfalls to Avoid

Do NOT apply hemochromatosis management strategies to CKD patients. 2 Venesection guidelines targeting ferritin <50 µg/L are completely inappropriate for ESRD patients who require ferritin >200 ng/mL to support erythropoiesis. 2

Do NOT withhold iron solely based on elevated ferritin if TSAT remains low, as this represents functional iron deficiency requiring treatment. 2, 5

Do NOT assume ferritin >500 ng/mL indicates iron overload without considering inflammatory status and TSAT. 2, 3 Moderate hyperferritinemia (500-2000 ng/mL) is usually due to inflammation, malnutrition, liver disease, or infection rather than iron excess. 3

Safety Considerations

Monitor patients for 60 minutes after initial IV iron administration with resuscitative facilities and trained personnel available. 1, 6 This applies to both iron dextran (stronger recommendation) and non-dextran formulations. 1

Exercise caution with IV iron during active infections, though many patients will still benefit from therapy. 1, 6