What causes a dialysis patient not to respond to Mercera (Epoetin)?

Causes of Non-Response to Epoetin (Mercera) in Dialysis Patients

The most common cause of inadequate response to Epoetin in dialysis patients is iron deficiency, followed by infection/inflammation, chronic blood loss, and osteitis fibrosa. 1

Primary Causes of Epoetin Resistance

1. Iron Deficiency

• Most frequent cause of hyporesponsiveness to Epoetin therapy 1, 2
• Affects more than 50% of dialysis patients 2
• Dialysis patients lose approximately 1.5-3 grams of iron per year 2
• Evaluation:
  • Check serum ferritin (target >100 ng/mL)
  • Check transferrin saturation (TSAT) (target >20%) 3

2. Infection and Inflammation

• Markedly impairs responsiveness to Epoetin 1
• Inflammatory cytokines (tumor necrosis factor, interleukin-1) inhibit erythropoiesis 1
• Elevated C-reactive protein levels predict resistance to Epoetin 1
• Common sources:
  • Access infections
  • Peritonitis (especially in CAPD patients)
  • AIDS
  • Rheumatologic disorders (e.g., SLE)
  • Surgical inflammation 1

3. Chronic Blood Loss

• Results in iron deficiency and impaired Epoetin response 1
• Suspect in patients who:
  • Require increasing doses to maintain stable hemoglobin
  • Have falling hemoglobin levels
  • Fail to augment iron stores despite IV iron supplementation 1

4. Osteitis Fibrosa (Secondary Hyperparathyroidism)

• Replaces active marrow erythroid elements with fibrosis
• Direct relationship between degree of fibrosis and amount of Epoetin needed 1

Less Common Causes

5. Aluminum Toxicity

• Can prolong time to reach target hemoglobin
• May necessitate higher Epoetin doses 1

6. Hemoglobinopathies

• Sickle cell disease patients respond poorly to Epoetin
• Alpha and beta thalassemia may require very high doses over long periods 1

7. Folate or Vitamin B12 Deficiency

• Essential for optimal hemoglobin synthesis
• Folate is water-soluble; dialysate losses may exceed intake in malnourished patients 1

8. Multiple Myeloma

• Can impair bone marrow response to Epoetin 1

9. Malnutrition

• Contributes to poor response to Epoetin therapy 1

10. Hemolysis

• Reduces effectiveness of Epoetin by shortening red blood cell lifespan 1

Diagnostic Approach

1. First step: Evaluate iron status (most common cause)

   • Serum ferritin (target >100 ng/mL)
   • Transferrin saturation (target >20%) 3

2. If iron-replete: Check for infection/inflammation

   • Complete blood count
   • C-reactive protein
   • Evaluate for access infections, peritonitis, or other inflammatory conditions 1

3. If no infection/inflammation: Evaluate for chronic blood loss

   • Occult gastrointestinal bleeding
   • Blood loss during dialysis
   • Other sources of bleeding 1

4. If no blood loss: Check parathyroid hormone levels for secondary hyperparathyroidism 1

5. If all above negative: Consider less common causes

   • Aluminum levels
   • Hemoglobinopathy screening
   • Folate and vitamin B12 levels
   • Evaluation for multiple myeloma
   • Nutritional assessment
   • Hemolysis workup 1

Management Strategies

1. Iron deficiency:

   • IV iron supplementation is more effective than oral iron in ESRD patients 4
   • Consider ferric gluconate if previous reaction to iron dextran 5

2. Infection/inflammation:

   • Identify and treat underlying infection
   • Responsiveness usually restored upon resolution 1

3. Chronic blood loss:

   • Identify and address source of bleeding
   • Replenish iron stores 1

4. Secondary hyperparathyroidism:

   • Treat underlying condition
   • Monitor calcium, phosphorus, and iPTH every three months 3

5. During intercurrent illness:

   • Continue Epoetin at a dose at least equal to pre-illness dose
   • Allows for more prompt resumption of erythropoiesis once illness resolves 1

Common Pitfalls to Avoid

• Continuing ineffective ESA therapy for more than 6-8 weeks without reevaluation 3
• Ignoring blood pressure control during Epoetin therapy 3
• Failing to check iron status as the first step in evaluation 1, 2
• Overlooking occult infection or inflammation 1
• Using transferrin saturation index alone for iron deficiency diagnosis 6
• Withholding IV iron during inflammation (should only be withheld during acute infection) 4

Remember that 96% of patients will respond to adequate doses of Epoetin within 4-6 months if all underlying causes of resistance are addressed 1.