From the Guidelines
Decreased erythropoietin (EPO) production is primarily caused by chronic kidney disease (CKD), as the kidneys are responsible for producing about 90% of the body's EPO, as stated in the guidelines by the National Kidney Foundation 1. Other causes of decreased EPO production include:
- Inflammatory conditions
- Malnutrition
- Hypothyroidism
- Certain medications
- Iron deficiency
- Severe hyperparathyroidism
- Aluminum toxicity
- Folate deficiency
- Shortened red blood cell survival
- Hemoglobinopathies such as thalassemia
Management of decreased EPO production focuses on treating the underlying cause and administering exogenous EPO replacement therapy. For CKD patients, recombinant human erythropoietin (rHuEPO) medications like epoetin alfa (Epogen, Procrit) at 50-100 units/kg three times weekly or darbepoetin alfa (Aranesp) at 0.45 μg/kg weekly are commonly prescribed, as recommended in the guidelines 1. Dosing is individualized to achieve and maintain hemoglobin levels between 10-12 g/dL, avoiding higher targets due to cardiovascular risk, as suggested by the study on cancer-related anemia 1. Concurrent iron supplementation is essential, with oral ferrous sulfate 325 mg three times daily or IV iron (such as iron sucrose or ferric carboxymaltose) for those with poor oral absorption, as recommended in the guidelines for anemia of chronic kidney disease 1. Regular monitoring of hemoglobin, iron studies, and kidney function is necessary to adjust therapy. EPO replacement works by stimulating red blood cell production in the bone marrow, compensating for the body's inability to produce adequate endogenous EPO and thereby improving anemia symptoms like fatigue, weakness, and reduced exercise tolerance.
From the Research
Causes of Decreased EPO Production
- Chronic kidney disease (CKD) is a major cause of decreased erythropoietin (EPO) production, as the kidneys are the primary site of EPO production 2, 3, 4.
- In CKD, pericytes in the kidneys transdifferentiate to myofibroblasts, leading to a decrease in EPO production 3.
- Anemia and hypoxia can stimulate EPO production, but in CKD, this response is impaired 3.
- Inflammation and increased hepcidin levels can also contribute to decreased EPO production and anemia in CKD patients 4.
Management of Decreased EPO Production
- Erythropoiesis stimulating agents (ESAs) such as recombinant human EPO (rhEPO) and darbepoetin alfa can be used to substitute for decreased EPO production 2, 5, 6.
- ESAs can improve hemoglobin levels, reduce the need for blood transfusions, and improve quality of life in CKD patients 2, 5.
- Iron supplements can also be used to manage anemia in CKD patients, as iron deficiency is common in this population 4.
- Newer therapies such as hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have shown promise in increasing EPO production and improving anemia in CKD patients 3, 4.