What is the appropriate management of anemia in a 75‑year‑old man with end‑stage renal disease on hemodialysis and a hemoglobin of 8.6 g/dL?

Management of Anemia in a 75-Year-Old Male on Hemodialysis with Hemoglobin 8.6 g/dL

Immediately initiate erythropoiesis-stimulating agent (ESA) therapy targeting hemoglobin 11–12 g/dL, but only after confirming adequate iron stores (TSAT ≥20%, ferritin ≥100 ng/mL) or starting intravenous iron concurrently if iron parameters are deficient. 1, 2

Step 1: Assess Iron Status Before or Concurrent with ESA Initiation

• Measure transferrin saturation (TSAT) and serum ferritin immediately to determine if iron stores are adequate for erythropoiesis. 1, 3
• Target iron parameters for hemodialysis patients are TSAT ≥20% and ferritin ≥100 ng/mL (optimally ≥200 ng/mL for best ESA response). 1, 2, 3
• If TSAT <20% or ferritin <100 ng/mL, start intravenous (IV) iron immediately; oral iron is ineffective in hemodialysis due to dialyzer blood losses (~400 mg iron every 3 months) and hepcidin-mediated absorption blockade. 1
• Do not delay ESA therapy while correcting iron deficiency—you can administer IV iron loading concurrently with ESA initiation in this symptomatic patient with hemoglobin 8.6 g/dL. 1, 2

Step 2: Initiate ESA Therapy

• Begin ESA therapy now because hemoglobin 8.6 g/dL is below the 9–10 g/dL threshold and is associated with higher morbidity and transfusion risk. 1, 2
• Start epoetin alfa at 150–300 IU/kg/week (typically 50–150 IU/kg per dose given 2–3 times weekly) via the intravenous route, which is preferred for hemodialysis patients. 1, 2, 3
• Alternatively, darbepoetin alfa may be initiated at 0.45 mcg/kg IV weekly or 0.75 mcg/kg every 2 weeks, taking advantage of its longer half-life. 1, 3
• Target a hemoglobin rise of 1.0–2.0 g/dL per month to reach the goal range of 11–12 g/dL. 2

Step 3: Maintain Iron Stores During ESA Therapy

• After initial iron repletion, provide maintenance IV iron at 25–125 mg weekly (e.g., iron sucrose) to replace ongoing dialysis-related iron losses of approximately 400–500 mg every 3 months. 1
• Functional iron deficiency (TSAT <20% despite ferritin 100–800 ng/mL) is common during ESA therapy and warrants continued IV iron supplementation. 1, 4
• Withhold IV iron when ferritin exceeds 800 ng/mL or TSAT exceeds 50%, as further supplementation offers no benefit and may raise infection risk. 1, 4

Step 4: Monitor Hemoglobin and Adjust ESA Dose

• Check hemoglobin weekly until stable, then at least monthly once the patient reaches target range. 1, 3
• Measure hemoglobin predialysis before the midweek session to avoid variability from ultrafiltration and the longer interdialytic interval. 5
• Reduce ESA dose by 25% if hemoglobin rises >1 g/dL within 2 weeks or exceeds 12 g/dL; interrupt the dose temporarily if hemoglobin approaches or exceeds 12 g/dL. 1, 2, 3
• Increase ESA dose by 25% if hemoglobin fails to rise ≥1 g/dL after 4 weeks of therapy despite confirmed adequate iron stores. 1, 2
• Do not adjust ESA doses more frequently than every 2–4 weeks to allow time for erythropoietic response. 2, 3

Step 5: Target Hemoglobin Range and Safety Thresholds

• Maintain hemoglobin between 11–12 g/dL (hematocrit 33–36%); this range balances symptom relief with cardiovascular safety. 1, 2, 3
• Do not target hemoglobin >12 g/dL—the CREATE and CHOIR trials demonstrated a 17% increase in mortality risk and 34% increase in arteriovenous access thrombosis with higher targets. 1, 2
• If hemoglobin exceeds 12.5 g/dL on a 3-month rolling average, reduce the ESA dose immediately and document medical justification for any continued therapy. 1

Step 6: Monitor Blood Pressure and Manage Hypertension

• Check blood pressure at every dialysis session because approximately 35% of patients develop hypertension during ESA therapy; rapid hemoglobin rises can precipitate seizures in about 5% of patients. 1, 2
• Adjust antihypertensive medications as needed to maintain blood pressure control during ESA therapy. 2

Step 7: Evaluate for ESA Hyporesponsiveness if Inadequate Response

• ESA hyporesponsiveness is defined as failure to achieve hemoglobin ≥11 g/dL despite epoetin alfa doses >300 IU/kg/week or darbepoetin alfa >1.5 mcg/kg/week. 1
• The most frequent cause of hyporesponsiveness is iron deficiency (functional or absolute); re-check TSAT and ferritin before escalating ESA doses. 1, 2
• If hemoglobin does not increase by >1 g/dL after a 12-week escalation period, further dose increases are unlikely to improve response and may increase risks—evaluate for other causes of anemia including chronic inflammation, infection, inadequate dialysis, hyperparathyroidism, aluminum toxicity, hemoglobinopathies, or pure red cell aplasia. 1, 2, 3

Critical Pitfalls to Avoid

• Do not administer IV iron during active infection; defer iron therapy until the infection resolves to avoid promoting bacterial growth. 1
• Do not continue oral iron in hemodialysis patients; more than 50% of ESRD patients receiving ESAs remain iron-deficient despite oral supplementation, making IV iron essential. 1
• Do not transfuse red blood cells unless immediate correction is needed (e.g., symptomatic anemia with cardiovascular instability), as ESAs take weeks to show effect but avoid the risks of alloimmunization and transfusion reactions. 2
• Do not use ESAs in patients with active malignancy, recent stroke, or severe uncontrolled hypertension without careful risk-benefit assessment. 2

Monitoring Schedule Summary

• Hemoglobin: Weekly until stable, then monthly 1, 3
• Iron parameters (TSAT, ferritin): Every 3 months once stable 4
• Blood pressure: Every dialysis session 1, 2