Anemia of CKD is More Than Just an EPO and Iron Deficiency

Multiple Pathophysiologic Factors Play a Role in Anemia of CKD1

Multiple Pathophysiologic Factors for Anemia of CKD

CKD=chronic kidney disease; EPO=erythropoietin.

  • The complex pathology of CKD includes a number of mechanisms that suppress red blood cell (RBC) production, including1:
    • Impaired oxygen sensing in the kidneys
    • Inflammation
    • Elevated hepcidin levels
  • Blood loss and decreased RBC survival also contribute to anemia of CKD1

Impaired Oxygen Sensing in the Kidneys Reduces EPO Production1,2,4,5

Impaired Oxygen Sensing in the Kidneys reduces EPO Production

HIF=hypoxia-inducible factor; O2=oxygen.

Data derived from pre-clinical mouse models.

  • In CKD, the normal oxygen-sensing mechanism in the kidneys is impaired. This results in insufficient HIF signaling in the kidneys1,2
  • Insufficient HIF signaling leads to decreased EPO production1,2,4,5
  • Iron absorption and availability is compromised4,5
  • As a result, anemia may develop1,2

Inflammation Suppresses RBC Production1

Chronic inflammation Suppresses RBC Production Chronic inflammation Suppresses RBC Production

Based on in vitro or observational studies or animal models.

  • Increased inflammation is associated with declining kidney function6
  • Inflammation contributes to anemia via1:
    • Suppressed endogenous EPO production
    • Impaired proliferation and differentiation of erythroid progenitors
    • Decreased life span of RBCs
    • Reduced iron absorption and availability due to increased hepcidin levels
  • These physiologic changes ultimately result in decreased erythropoiesis1

Elevated Hepcidin Levels Restrict Iron Absorption and Availability1

Elevated Hepcidin Levels Restrict Iron Absorption and Availability Elevated Hepcidin Levels Restrict Iron Absorption and Availability

Based on in vitro and animal models.

  • Hepcidin is a liver-derived hormone that serves as the key regulator of iron homeostasis in the body1
  • Hepcidin maintains the balance of iron by the degradation of ferroportin, a transporter protein responsible for moving iron out of cellular storage sites and into the body’s circulation for use1
  • When hepcidin is elevated, iron is sequestered—or trapped—in the storage cells. Therefore, iron is unable to be used for erythropoiesis, which may lead to functional iron deficiency1,7

Functional and absolute iron deficiency

  • Functional iron deficiency:
    • A state in which, despite adequate or increased iron stores in the body, iron is not available due to insufficient mobilization to be incorporated into maturing RBCs7,8
    • Characterized by low transferrin saturation with normal or elevated ferritin9,10
  • Absolute iron deficiency:
    • A state in which there are low iron stores in the body1,8
    • Characterized by low transferrin saturation and low ferritin levels9

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