Primary Cause of Anemia in Chronic Kidney Disease
The primary cause of anemia in patients with Chronic Kidney Disease (CKD) is insufficient production of erythropoietin (EPO) by the diseased kidneys. 1
Pathophysiology of Anemia in CKD
- Normocytic, normochromic anemia is present in the majority of patients with reduced kidney function 1
- As kidney function declines, the likelihood of anemia associated with EPO deficiency increases because the diseased kidneys are unable to produce sufficient quantities of EPO 1
- Anemia can develop relatively early in the course of CKD, with significant anemia noted when GFR falls below 20-35 mL/min/1.73 m² 1
- The failing kidneys cannot produce adequate erythropoietin to stimulate bone marrow to produce red blood cells 2
Additional Contributing Factors to Anemia in CKD
While EPO deficiency is the primary cause, several other factors may contribute to anemia in CKD patients:
- Iron deficiency (related to blood loss from laboratory testing, dialysis, or gastrointestinal bleeding) 1
- Severe hyperparathyroidism 1, 3
- Acute and chronic inflammatory conditions 1
- Aluminum toxicity 1, 3
- Folate deficiency 1
- Shortened red blood cell survival 1, 3
- Hypothyroidism 1
- Hemoglobinopathies such as thalassemia 1
Clinical Significance
- When untreated, anemia of CKD is associated with numerous physiologic abnormalities 1:
- Decreased tissue oxygen delivery and utilization
- Increased cardiac output and cardiac enlargement
- Ventricular hypertrophy
- Angina and congestive heart failure
- Decreased cognition and mental acuity
- Impaired immune responsiveness
- Anemia is a risk factor for cardiovascular disease and is associated with higher rates of hospitalization and mortality 2
Diagnosis and Management
- Anemia should be suspected in CKD patients with GFR <60 mL/min/1.73 m² 2
- Diagnosis is made when hemoglobin is <12 g/dL in men or postmenopausal women, or <11 g/dL in premenopausal women 2
- After excluding other causes of anemia, treatment with erythropoiesis-stimulating agents (ESAs) is indicated 2
- Adequate iron stores (transferrin saturation >20% and ferritin >100 mg) must be maintained for effective ESA therapy 2
- The optimal target hemoglobin level is ≥11 g/dL 4
Common Pitfalls
- Anemia in CKD is often under-recognized and undertreated, with approximately 75% of patients initiating dialysis having hemoglobin <11 g/dL 2
- Failing to distinguish between anemia of CKD and anemia of chronic disease (in the latter, inflammatory cytokines suppress EPO production and erythropoiesis directly) 1
- Not investigating other potential causes of anemia before attributing it solely to CKD 1
- Inadequate iron supplementation, which can limit response to ESA therapy 2