CAUSES OF IRON DEFICIENCY ANEMIA IN
NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE

Absolute (true) versus functional iron deficiency:

Absolute

Severely diminished or non-existent iron stores in the bone marrow, liver, and spleen

Functional

Normal or increased iron reserves that cannot be converted into erythroid precursors for erythropoiesis

Hepcidin and Ferroportin

Hepcidin, secreted by the liver, plays a major role in regulating iron metabolism. Hepcidin blocks the movement of iron by attaching to the ferroportin iron transporter, which is found on the basal membrane of enterocytes, reticuloendothelial cells, and hepatocytes. Ferroportin is internalized by the cell after interacting with hepcidin, leading to its eventual destruction. Hepcidin prevents iron from being absorbed or regenerated by reticuloendothelial cells, which lowers the level of iron in the blood.1
Figure 1: Hepcidin and ferroportin interact to regulate the flow of iron into plasma2
Chronic kidney disease (CKD) causes a rise in hepcidin levels, which are inversely linked with glomerular filtration rate (GFR). This condition in CKD is caused by:
  • decreased renal clearance.1
  • elevated inflammatory cytokines.1
  • decreased erythropoietin levels.1

A high rate of iron loss (1-3g/year) is also a result of:

  • Gastrointestinal bleeding brought on by platelet dysfunction and gastritis [in both non-dialysis-dependent (NDD) and dialysis-de- pendent (DD) CKD]1
  • Gastrointestinal bleeding brought on by platelet dysfunction and gastritis [in both non-dialysis-dependent (NDD) and dialysis-de- pendent (DD) CKD]1
  • Malnutrition and decreased gastrointestinal iron absorption1
Iron deficiency is widespread among CKD patients who are NDD and DD because of the concomitant reduction in iron absorption and increase in iron losses.1

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REFERENCES:

  1. Gafter-Gvili A, Schechter A, Rozen-Zvi B. Iron Deficiency Anemia in Chronic Kidney Disease. Acta Haematol. 2019;142(1):44-50. doi: 10.1159/000496492. Epub 2019.
  2. Nemeth E, Ganz T. Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeo-stasis. Int J Mol Sci. 2021;22(12):6493. doi: 10.3390/ijms22126493.