How to manage and evaluate anemia in Chronic Kidney Disease (CKD)?

Management and Evaluation of Anemia in Chronic Kidney Disease

Anemia in CKD requires systematic evaluation of hemoglobin levels, iron status, and appropriate therapy with iron supplementation and/or erythropoiesis-stimulating agents (ESAs), with the primary goal of reducing transfusion needs while avoiding cardiovascular risks associated with aggressive treatment. 1

Diagnosis and Initial Evaluation

• Diagnose anemia when hemoglobin is <135 g/L in adult males or <120 g/L in adult females with CKD 1
• Screen all CKD patients for anemia at least annually; more frequent monitoring is needed for diabetic patients who develop anemia earlier and have higher prevalence of anemia at any level of kidney function 1
• Initial evaluation should include:
  • Complete blood count (hemoglobin, white blood cells, platelets) to assess bone marrow function 1
  • Reticulocyte count to evaluate bone marrow response to anemia 1
  • Iron studies including serum ferritin and transferrin saturation (TSAT) 1
  • Assessment for other causes of anemia (B12, folate deficiency, blood loss) 1

Iron Status Assessment

• Hemoglobin is preferred over hematocrit for monitoring anemia due to better reproducibility across laboratories and less susceptibility to storage time and patient variables 1
• Evaluate iron status using:
  • Serum ferritin (marker for tissue iron stores) 1
  • Transferrin saturation (TSAT) (represents iron available for erythropoiesis) 1
  • Mean corpuscular volume (late marker of iron deficiency) 1
• Define absolute iron deficiency in CKD as:
  • TSAT ≤20% and ferritin ≤100 ng/mL in non-dialysis CKD patients 2
  • TSAT ≤20% and ferritin ≤200 ng/mL in hemodialysis patients 2
• Functional iron deficiency is characterized by TSAT ≤20% with elevated ferritin levels 2
• Consider inflammation's impact on ferritin (an acute phase reactant); C-reactive protein measurement may help interpret elevated ferritin levels 1

Iron Management

• Evaluate iron status in all patients before and during treatment 3, 4
• Administer supplemental iron when serum ferritin is <100 mcg/L or TSAT is <20% 3, 4
• Most CKD patients will require supplemental iron during ESA therapy 3, 4
• For non-dialysis CKD patients (stages 3-5), either IV or oral iron supplementation is appropriate 2
• For hemodialysis patients (CKD stage 5D), IV iron is preferred over oral iron 2
• In patients with low baseline ferritin (<100 ng/ml), IV iron produces greater hemoglobin increases compared to oral iron 5
• IV iron sucrose (200 mg weekly) has been shown to be effective and safe in CKD patients not on dialysis 5

ESA Therapy

• Use the lowest ESA dose sufficient to reduce the need for red blood cell transfusions 3, 4
• Initiate ESA treatment in dialysis patients when hemoglobin is <10 g/dL 3, 4
• For non-dialysis CKD patients, consider initiating ESA only when hemoglobin is <10 g/dL and:
  • The rate of hemoglobin decline indicates likely need for transfusion
  • Reducing risk of alloimmunization and/or other transfusion-related risks is a goal 3
• Do not target hemoglobin levels >11 g/dL with ESAs due to increased risks of death, serious adverse cardiovascular reactions, and stroke 3, 4
• Monitor hemoglobin weekly after initiating therapy or dose adjustments until stable, then monthly 3, 4
• Avoid frequent dose adjustments; do not increase dose more than once every 4 weeks 3, 4
• Reduce ESA dose by 25% or more if hemoglobin rises rapidly (>1 g/dL in any 2-week period) 3, 4

Monitoring Response to Therapy

• After initiating therapy and after each dose adjustment, monitor hemoglobin weekly until stable, then at least monthly 3, 4
• For hemodialysis patients, measure hemoglobin before the midweek dialysis session to avoid variability from ultrafiltration 1
• If hemoglobin has not increased by >1 g/dL after 4 weeks of therapy, increase dose by 25% 3, 4
• If no adequate response after 12 weeks of escalation, further dose increases are unlikely to improve response and may increase risks 3, 4
• Consider discontinuation of ESA if responsiveness does not improve despite adequate iron stores 3, 4

Special Considerations

• Patients with diabetes require more vigilant monitoring due to earlier onset and higher prevalence of anemia at any level of kidney function 1
• In non-dialysis CKD patients with iron deficiency but without known causes of blood loss, evaluate for gastrointestinal bleeding 1
• Consider inflammation as a cause of ESA resistance and functional iron deficiency 1, 6
• Newer approaches including hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs) are emerging as alternatives to traditional ESA therapy 1, 7

Pitfalls to Avoid

• Do not rely solely on ferritin and TSAT for iron status assessment in inflammatory states 1
• Avoid targeting hemoglobin levels >11 g/dL with ESAs due to increased cardiovascular risks 3, 4
• Do not overlook non-renal causes of anemia in CKD patients 1
• Avoid frequent ESA dose adjustments based on single hemoglobin measurements 3, 4
• Do not continue escalating ESA doses in non-responders beyond 12 weeks 3, 4