What is the initial treatment approach for anemia in patients with Chronic Kidney Disease (CKD)?

Initial Treatment Approach for Anemia in CKD

The initial treatment for anemia in CKD begins with iron supplementation—not ESAs—after correcting all other causes of anemia and ensuring adequate iron stores are evaluated and optimized. 1

Step 1: Evaluate and Correct All Causes Before Treatment

Before initiating any anemia therapy, you must address all correctable causes of anemia including iron deficiency, inflammatory states, vitamin B12 and folate deficiencies, bleeding, and metabolic conditions 1. The KDIGO guidelines explicitly state to "address all correctable causes of anemia (including iron deficiency and inflammatory states) prior to initiation of ESA therapy" 1.

Initial laboratory evaluation must include: 1

• Complete blood count with red cell indices, white blood cell count with differential, and platelet count
• Absolute reticulocyte count
• Serum ferritin level
• Transferrin saturation (TSAT)
• Serum vitamin B12 and folate levels

Step 2: Iron Supplementation as First-Line Therapy

For Adult CKD Patients NOT on Dialysis (Stages 3-5):

Initiate a trial of IV iron (or alternatively a 1-3 month trial of oral iron) when: 1

• An increase in hemoglobin without starting ESA treatment is desired AND
• TSAT is ≤30% AND ferritin is ≤500 ng/mL

The route of iron administration should be selected based on severity of iron deficiency, venous access availability, prior response to oral iron, side effects with previous iron therapy, patient compliance, and cost 1. However, IV iron is generally more effective than oral iron for achieving hemoglobin response in CKD stages 3-5, with patients 1.61 times more likely to reach a hemoglobin increase >1 g/dL compared to oral iron 2.

For Adult CKD Patients on Hemodialysis (Stage 5D):

Administer IV iron when: 1

• TSAT is ≤30% AND ferritin is ≤500 ng/mL (if not on ESA therapy)
• TSAT is ≤30% AND ferritin is ≤500 ng/mL (if on ESA therapy and seeking to increase hemoglobin or decrease ESA dose)

IV iron is strongly preferred over oral iron in hemodialysis patients, with patients 2.14 times more likely to achieve hemoglobin response >1 g/dL 2.

For Pediatric CKD Patients:

Administer oral iron (or IV iron in hemodialysis patients) when: 1

• TSAT is ≤20% AND ferritin is ≤100 ng/mL (if not on ESA therapy)
• To maintain TSAT >20% AND ferritin >100 ng/mL (if on ESA therapy)

Step 3: Iron Status Monitoring

Evaluate iron status (TSAT and ferritin) at least every 3 months during treatment 1. Test more frequently when initiating therapy, when there is blood loss, after IV iron administration, or when iron stores may become depleted 1.

Before and during all ESA therapy, evaluate iron status and administer supplemental iron when serum ferritin is <100 mcg/L or TSAT is <20% 3, 4. The majority of CKD patients will require supplemental iron during ESA therapy 1, 4.

Step 4: When to Consider ESA Therapy

ESAs should only be considered after addressing iron deficiency and other correctable causes 1.

For Adult CKD Patients NOT on Dialysis:

Do NOT initiate ESA therapy if hemoglobin is ≥10.0 g/dL 1.

For hemoglobin <10.0 g/dL, individualize the decision based on: 1

• Rate of hemoglobin decline
• Prior response to iron therapy
• Risk of requiring transfusion
• Risks related to ESA therapy (stroke, vascular access loss, hypertension)
• Presence of anemia-related symptoms

For Adult CKD Patients on Dialysis (Stage 5D):

Start ESA therapy when hemoglobin is between 9.0-10.0 g/dL to avoid falling below 9.0 g/dL 1.

Critical ESA Safety Considerations:

Use ESAs with great caution or avoid entirely in patients with: 1

• Active malignancy (especially when cure is anticipated)
• History of stroke
• History of malignancy

Never use ESAs to intentionally increase hemoglobin above 13 g/dL in adults 1. In general, do not maintain hemoglobin above 11.5 g/dL, as targeting higher levels increases risks of death, serious cardiovascular events, and stroke without improving quality of life 1, 3, 4.

Step 5: Safety Monitoring for IV Iron

When administering IV iron dextran, monitor patients for 60 minutes after infusion with resuscitative facilities and trained personnel available 1. For non-dextran IV iron formulations, similar monitoring is suggested 1.

Common Pitfalls to Avoid:

• Do not start ESAs before optimizing iron stores—this is the most common error and leads to ESA hyporesponsiveness 1, 5
• Do not target hemoglobin levels >11.5 g/dL—this increases mortality and cardiovascular risks without benefit 1, 3
• Do not overlook inflammation as a cause of ESA hyporesponsiveness—inflammation increases hepcidin and restricts iron availability 5, 6
• Do not use oral iron alone in hemodialysis patients—IV iron is significantly more effective 2