When to use erythropoiesis-stimulating agents (ESAs) versus iron replacement versus blood transfusion in an older patient with chronic kidney disease (CKD) and chronic anemia without bleeding?

Management of Anemia in Elderly Patients with CKD

For elderly patients with CKD and chronic anemia without bleeding, first assess iron status and provide IV iron if deficient (TSAT ≤30% and ferritin ≤500 ng/ml), then consider ESAs if hemoglobin remains <10 g/dL despite iron repletion, and reserve transfusions only for severe symptomatic anemia or when rapid correction is needed.

Initial Assessment

Before initiating any treatment, a complete evaluation of anemia is essential:

• Complete blood count with red cell indices
• Absolute reticulocyte count
• Serum ferritin level
• Transferrin saturation (TSAT)
• Serum vitamin B12 and folate levels 1

Iron Therapy

Iron deficiency is a common cause of anemia in CKD patients and should be addressed first:

When to use iron:

• For patients not on ESA therapy: Use IV iron (or oral iron for non-dialysis CKD) when:

  • TSAT is ≤30% and ferritin is ≤500 ng/ml
  • An increase in hemoglobin is desired without starting ESA 1

• For patients on ESA therapy: Use IV iron (or oral iron for non-dialysis CKD) when:

  • TSAT is ≤30% and ferritin is ≤500 ng/ml
  • An increase in hemoglobin or decrease in ESA dose is desired 1

Iron administration:

• IV iron is preferred for hemodialysis patients
• For non-dialysis CKD patients, either IV iron or a 1-3 month trial of oral iron can be used
• Route selection should be based on:
  • Severity of iron deficiency
  • Venous access availability
  • Response to prior iron therapy
  • Side effects
  • Patient compliance
  • Cost 1

Erythropoiesis-Stimulating Agents (ESAs)

When to use ESAs:

• Only after addressing iron deficiency and other correctable causes of anemia
• For adult CKD non-dialysis patients with Hb <10.0 g/dL, consider ESA therapy based on:
  • Rate of fall of Hb concentration
  • Prior response to iron therapy
  • Risk of needing transfusion
  • Presence of anemia-related symptoms 1

Cautions with ESA therapy:

• Use with great caution in patients with:
  • Active malignancy
  • History of stroke
  • History of malignancy 1
• Monitor response within 6-8 weeks and discontinue if no response 1
• Target hemoglobin should be the lowest concentration needed to avoid transfusions 1

Blood Transfusions

Reserve transfusions for:

• Severe symptomatic anemia
• When rapid correction of anemia is needed
• When other therapies have failed or are contraindicated

Monitoring

• For patients not on ESA: Check hemoglobin at least every 3 months for CKD stages 3-5
• For patients on ESA: Evaluate iron status (TSAT and ferritin) at least every 3 months
• Test iron status more frequently when:
  • Initiating or increasing ESA dose
  • After blood loss
  • After a course of IV iron
  • When iron stores may become depleted 1

Algorithm for Management

1. Assess iron status:

   • If TSAT ≤30% and ferritin ≤500 ng/ml → Provide iron supplementation
   • For hemodialysis patients → Use IV iron
   • For non-dialysis CKD → Try oral iron for 1-3 months; if ineffective or poorly tolerated, switch to IV iron

2. After iron repletion, if Hb remains <10 g/dL:

   • Consider ESA therapy if patient has symptoms of anemia
   • Balance benefits (avoiding transfusions, improving symptoms) against risks (stroke, hypertension)
   • Start with recommended doses and adjust based on response

3. If no response to ESA within 6-8 weeks:

   • Discontinue ESA
   • Reevaluate for other causes of anemia

4. For severe symptomatic anemia:

   • Consider blood transfusion

Common Pitfalls to Avoid

1. Ignoring iron deficiency: Many CKD patients have functional iron deficiency despite normal or high ferritin levels due to inflammation and hepcidin dysregulation 2

2. Targeting too high hemoglobin levels: Higher Hb targets with ESAs have been associated with increased cardiovascular events

3. Continuing ineffective ESA therapy: If no response after 6-8 weeks, discontinue and reassess 1

4. Overlooking concurrent iron supplementation with ESAs: Iron supplementation should be considered in all patients receiving ESAs, regardless of iron status, as it reduces ESA dose requirements 1

5. Relying solely on ferritin for iron status: Ferritin is an acute phase reactant and may be elevated in CKD due to inflammation despite iron deficiency 3

By following this structured approach, you can effectively manage anemia in elderly CKD patients while minimizing risks and optimizing outcomes related to morbidity, mortality, and quality of life.