What is the appropriate management of anemia in a 75‑year‑old patient with end‑stage renal disease on regular hemodialysis who has a hemoglobin of 8.6 g/dL (hematocrit 26.4%)?

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

This patient requires immediate initiation of intravenous iron supplementation and erythropoiesis-stimulating agent (ESA) therapy, as the hemoglobin of 8.6 g/dL is well below the target range of 11–12 g/dL for hemodialysis patients. 1, 2

Step 1: Assess and Optimize Iron Status Before ESA Initiation

Before starting or escalating ESA therapy, you must measure transferrin saturation (TSAT) and serum ferritin to confirm adequate iron availability for erythropoiesis. 1, 2, 3

• Target iron parameters for hemodialysis patients are TSAT ≥ 20% and ferritin ≥ 100 ng/mL (ideally ≥ 200 ng/mL for optimal ESA response). 1, 2, 4
• If TSAT < 20% or ferritin < 100 ng/mL, initiate intravenous iron immediately—oral iron is insufficient in hemodialysis patients due to ongoing dialyzer blood losses (approximately 400 mg iron lost every 3 months) and hepcidin-mediated absorption blockade. 1, 4

IV Iron Dosing Protocol for Hemodialysis Patients

• Administer iron sucrose 100 mg intravenously at 10 consecutive dialysis sessions (total 1,000 mg loading dose) to rapidly replete iron stores. 4, 5
• Do not recheck iron studies until at least 7 days after the final loading dose, as ferritin and TSAT are falsely elevated immediately post-infusion. 4
• After achieving target iron parameters, maintain with 25–125 mg iron sucrose weekly to replace ongoing dialysis-related losses (approximately 400–500 mg every 3 months). 1, 4
• Withhold IV iron if ferritin exceeds 800 ng/mL or TSAT exceeds 50%, as further supplementation provides no benefit and may increase infection risk. 1, 4

Step 2: Initiate ESA Therapy

Once iron stores are confirmed adequate (or simultaneously with IV iron loading), start an ESA to target hemoglobin 11–12 g/dL. 1, 2, 3

ESA Selection and Dosing

For hemodialysis patients, either epoetin alfa or darbepoetin alfa may be used; the intravenous route is preferred in hemodialysis. 1, 3

• Epoetin alfa: Start at 50–150 IU/kg intravenously 2–3 times per week (typical starting dose ~4,000–6,000 units three times weekly for a 75 kg patient). 2, 6, 7
• Darbepoetin alfa: Start at 0.45 mcg/kg intravenously once weekly or 0.75 mcg/kg every 2 weeks (typical starting dose ~30–35 mcg weekly for a 75 kg patient). 2, 3

ESA Dose Adjustment Algorithm

Monitor hemoglobin weekly until stable, then at least monthly. 2, 3

• If hemoglobin rises >1 g/dL within 2 weeks or exceeds 12 g/dL, reduce the ESA dose by 25%. 2, 3
• If hemoglobin fails to rise ≥1 g/dL after 4 weeks despite adequate iron stores (TSAT ≥ 20%, ferritin ≥ 100 ng/mL), increase the ESA dose by 25%. 2, 3
• Do not increase ESA doses more frequently than every 4 weeks; avoid frequent dose adjustments to prevent hemoglobin cycling. 3

Step 3: Target Hemoglobin Range and Safety Monitoring

Target hemoglobin 11–12 g/dL (hematocrit 33–36%); do not routinely target hemoglobin >12 g/dL, as higher targets increase mortality, cardiovascular events, and stroke risk without improving quality of life. 1, 2, 3

• If hemoglobin exceeds 12 g/dL, reduce or interrupt the ESA dose immediately. 1, 3
• Monitor blood pressure closely during ESA therapy, as 35% of patients experience hypertension; seizures occur in 5.4% of patients, particularly with rapid hemoglobin rises. 7
• Monitor serum creatinine and potassium levels, as both may increase modestly during ESA therapy. 6, 7

Step 4: Address ESA Hyporesponsiveness

If hemoglobin remains <11 g/dL despite epoetin alfa doses >300 IU/kg/week or darbepoetin alfa >1.5 mcg/kg/week, the patient is ESA-hyporesponsive. 2

The most common cause of ESA hyporesponsiveness is iron deficiency (functional or absolute)—recheck TSAT and ferritin before escalating ESA doses further. 2, 4

• Functional iron deficiency (TSAT <20% despite ferritin 100–800 ng/mL) is common during ESA therapy and warrants continued IV iron supplementation. 1, 2, 4
• Other causes of hyporesponsiveness include inadequate dialysis (urea reduction ratio <65%), chronic inflammation, hyperparathyroidism, aluminum toxicity, occult blood loss, and myelofibrosis. 8, 9, 7
• Increasing dialysis adequacy (urea reduction ratio from 60% to 72%) can raise hematocrit by 4 percentage points independent of ESA dose. 8

Step 5: Ongoing Monitoring Schedule

• Hemoglobin: Weekly until stable, then monthly. 2, 3
• TSAT and ferritin: Every 3 months once iron repletion is achieved. 2, 4
• Blood pressure: At every dialysis session during ESA therapy. 7

Critical Pitfalls to Avoid

• Do not assume normal ferritin indicates adequate iron; ferritin is an acute-phase reactant and may be falsely elevated by inflammation—always interpret it together with TSAT. 4
• Do not continue oral iron in hemodialysis patients; more than 50% of ESRD patients receiving ESAs are iron deficient despite oral supplementation, and IV iron is required to maintain adequate stores. 1, 4
• Do not target hemoglobin >12 g/dL; the CREATE and CHOIR trials demonstrated increased mortality (risk ratio 1.17) and arteriovenous access thrombosis (risk ratio 1.34) with higher hemoglobin targets. 1
• Do not administer IV iron during active infection; withhold iron therapy until infection resolves, as iron may exacerbate bacterial growth. 1, 4, 10
• Do not delay ESA initiation in symptomatic anemia; this patient's hemoglobin of 8.6 g/dL is associated with increased morbidity and transfusion risk. 1