Anemia Type in Chronic Kidney Disease
The anemia of CKD is normocytic normochromic anemia, primarily caused by inadequate erythropoietin production from failing kidneys, with iron deficiency (both absolute and functional) as a major contributing factor. 1, 2, 3
Pathophysiology and Classification
The anemia develops through multiple mechanisms that distinguish it from other anemia types:
Primary Mechanism
- Erythropoietin deficiency is the dominant cause, as diseased kidneys fail to produce adequate EPO in response to hypoxia 4, 3, 5
- This results in normocytic normochromic red blood cells with inadequate bone marrow stimulation 2, 3
Iron Deficiency Component
CKD patients develop two distinct types of iron deficiency that complicate the anemia 1:
Absolute Iron Deficiency:
- Transferrin saturation ≤20% with ferritin ≤100 μg/L (predialysis/peritoneal dialysis patients) 1, 6
- Transferrin saturation ≤20% with ferritin ≤200 μg/L (hemodialysis patients) 1, 6
Functional Iron Deficiency:
- Transferrin saturation ≤20% with elevated ferritin levels (>100-200 μg/L depending on dialysis status) 1
- Iron stores are adequate but unavailable for erythropoiesis due to hepcidin-mediated sequestration 1
- This represents kinetic iron deficiency where demand exceeds supply during erythropoiesis 1
Additional Contributing Factors
- Shortened red blood cell survival and direct bone marrow suppression 1, 3
- Chronic inflammation causing hepcidin elevation and iron sequestration 1, 3
- Blood loss from dialysis, phlebotomy, or GI sources 1
- Reduced iron absorption from the gut due to elevated hepcidin 1
Diagnostic Approach
When to Screen
- All CKD patients should undergo hemoglobin testing regardless of stage or cause 1
- Screen at least annually, with more frequent monitoring for diabetic patients 7
- Anemia prevalence increases dramatically when GFR <60 mL/min/1.73m² (Stage 3) and is nearly universal at Stage 5 1
Diagnostic Thresholds
Define anemia at these hemoglobin levels 1:
- <13.5 g/dL in adult males
- <12.0 g/dL in adult females
Essential Laboratory Workup
When anemia is identified, obtain 7:
- Complete blood count with reticulocyte count to assess bone marrow response
- Iron studies: serum ferritin and transferrin saturation
- Stool guaiac when iron deficiency is detected
- Vitamin B12 and folate if macrocytosis present
- C-reactive protein to evaluate inflammation when ferritin is elevated
Critical Interpretation Caveat
Ferritin is an acute-phase reactant and may be falsely elevated in inflammation despite true iron deficiency 1, 7. In inflammatory states, transferrin saturation becomes more reliable than ferritin alone 7. The diagnostic thresholds for iron deficiency in CKD differ substantially from the general population due to this complexity 1.
Management Implications
The normocytic normochromic nature with multifactorial etiology requires:
- Iron supplementation (IV preferred for dialysis patients) before or concurrent with ESA therapy 1, 8, 6
- Erythropoiesis-stimulating agents once hemoglobin falls below 9-10 g/dL 8
- Target hemoglobin 9-11.5 g/dL (never exceed 13 g/dL due to increased mortality risk) 8
- Exclude other causes including B12/folate deficiency, blood loss, hemoglobinopathies, and malignancy before attributing anemia solely to CKD 1, 7, 4
The distinction between absolute and functional iron deficiency is therapeutically critical, as functional iron deficiency may respond better to IV iron than oral supplementation due to hepcidin-mediated blockade of intestinal absorption 1, 6.