How is anemia caused by impaired renal (kidney) function typically treated?

Treatment of Anemia Caused by Chronic Kidney Disease

Treat anemia of chronic kidney disease with erythropoiesis-stimulating agents (ESAs) such as epoetin alfa or darbepoetin alfa, combined with iron supplementation, targeting hemoglobin levels of 10-11 g/dL—avoiding higher targets due to increased cardiovascular risks and mortality. 1, 2

Initial Assessment and Iron Repletion

Before initiating ESA therapy, you must evaluate and correct iron deficiency, as iron is essential for hemoglobin formation and most CKD patients will require supplemental iron during ESA therapy 1, 2:

• Measure iron status: Check serum ferritin and transferrin saturation (TSAT) before starting treatment 1, 2
• Initiate iron supplementation when: Ferritin <100 mcg/L OR TSAT <20% 2
• Define absolute iron deficiency as: TSAT <20% AND ferritin <100 mg/L (non-dialysis) or <200 mg/L (hemodialysis patients) 1
• Administer intravenous iron for dialysis patients; oral or IV iron for non-dialysis CKD patients 1

Critical pitfall: Inadequate iron stores are the most common cause of poor ESA response—always ensure iron repletion before escalating ESA doses 1, 2

Erythropoiesis-Stimulating Agent Therapy

When to Initiate ESAs

For dialysis patients: Start ESA when hemoglobin <10 g/dL 2

For non-dialysis CKD patients: Initiate only when hemoglobin <10 g/dL AND both of the following apply 2:

• The rate of hemoglobin decline indicates likelihood of requiring RBC transfusion
• Reducing alloimmunization risk or other transfusion-related risks is a treatment goal

Dosing Strategy

Darbepoetin alfa (preferred for less frequent dosing): 2

• Starting dose for dialysis patients: 0.45 mcg/kg IV or SC weekly, OR 0.75 mcg/kg every 2 weeks
• Starting dose for non-dialysis patients: 0.45 mcg/kg IV or SC every 4 weeks
• Route: Intravenous preferred for hemodialysis patients; either route acceptable for others 2

Epoetin alfa: Administered 2-3 times weekly; can be converted to darbepoetin for less frequent dosing 1

Hemoglobin Targets and Monitoring

Target hemoglobin range: 10-11 g/dL for dialysis patients; maintain <10 g/dL for non-dialysis patients 1, 2

Critical warning: Targeting hemoglobin >11 g/dL increases risks of death, serious cardiovascular events, and stroke 1, 2

Monitoring schedule: 2

• Check hemoglobin weekly after initiation or dose adjustment until stable
• Once stable, monitor monthly
• Evaluate iron parameters regularly throughout treatment 1, 2

Dose Adjustments

If hemoglobin rises rapidly (>1 g/dL in 2 weeks): Reduce dose by 25% or more 2

If hemoglobin increases <1 g/dL after 4 weeks: Increase dose by 25% 2

If no response after 12 weeks of dose escalation: Further increases unlikely to help and may increase risks—evaluate other causes of anemia and consider discontinuing 2

If hemoglobin approaches or exceeds target: Reduce or interrupt ESA dose 2

Key principle: Use the lowest ESA dose sufficient to reduce transfusion need; avoid frequent dose adjustments 2

Evaluate Contributing Factors

The primary cause is insufficient erythropoietin production by diseased kidneys, but multiple factors can contribute 1:

• Iron deficiency: From blood loss (laboratory testing, dialyzer retention, GI bleeding) 1
• Severe hyperparathyroidism 1
• Acute and chronic inflammatory conditions 1
• Aluminum toxicity 1
• Folate deficiency 1
• Shortened RBC survival 1
• Hypothyroidism 1
• Hemoglobinopathies (thalassemia) 1

Address these contributing factors before attributing poor response solely to ESA resistance 1

Novel Therapies: HIF-Prolyl Hydroxylase Inhibitors

Newer oral agents (roxadustat, vadadustat, daprodustat) are available in some regions and work by stabilizing hypoxia-inducible factors 1:

• Mechanism: Stimulate endogenous erythropoietin production and improve iron utilization by suppressing hepcidin 1
• Cardiovascular safety concerns: Some trials showed increased MACE risk compared to ESAs, particularly with vadadustat (HR 1.17) and roxadustat in on-treatment analyses (HR 1.38) 1
• Current status: Not yet widely recommended as first-line therapy pending additional safety data 1

Consequences of Untreated Anemia

Untreated anemia in CKD causes significant morbidity 1:

• Decreased tissue oxygen delivery
• Cardiac enlargement and ventricular hypertrophy
• Angina and congestive heart failure
• Decreased cognition and mental acuity
• Impaired immune function
• Growth retardation in children
• Reduced quality of life and survival 1

Special Considerations

Pediatric patients: Start darbepoetin at 0.45 mcg/kg SC or IV weekly; target hemoglobin <12 g/dL 2

Kidney transplant recipients: Same principles apply, but monitor for immunosuppressive medication effects on blood counts 3

ESA hyporesponders: Evaluate for iron deficiency, inflammation, infection, hyperparathyroidism, and medication effects before escalating doses 1