What is the role of iron deficiency in the diagnosis of anemia of chronic disease and renal failure?

Updated: Apr 13, 2020
  • Author: Gates B Colbert, MD, FASN; Chief Editor: Emmanuel C Besa, MD  more...
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As noted above, iron deficiency is the most common identifiable cause of ESA resistance. The 2 most important tests to order to assess iron deficiency are transferrin saturation (TSAT) and serum ferritin.

The importance of these tests lies in the fact that the diagnosis of iron deficiency anemia is not truly straightforward, as the possible etiologies include both insufficient iron stores (absolute iron deficiency) and insufficient release of stored iron by the reticuloendothelial tissues, so that too little iron is available for erythropoiesis (functional iron deficiency). [11]

Anemia of CKD tends to primarily involve functional iron deficiency. Traditionally, this is characterized by a TSAT less than 20% and a ferritin level less than 100 ng/mL; however, there is evidence that those cutoffs may not be sensitive to detect iron deficiency. In a study by Stancu et al in 100 patients with CKD (stages 3–5), those indices identified 17% of patients as iron deficient but bone marrow iron staining showed that 48% were iron deficient. [30]  Consequently, iron therapy should be considered in patients with CKD whose TSAT is ≤30%, as iron therapy has the potential to increase the hemoglobin concentration or permit a decrease in the ESA dose. [16]

Clinicians must also be aware that although a low ferritin level has high specificity for absolute iron deficiency, ferritin is an acute-phase reactant that can be elevated in states of chronic infection or inflammation. [30]  Therefore, an elevated ferritin does not necessarily imply iron store adequacy or overload. KDIGO guidelines recommend a trial of iron repletion if the serum ferritin is ≤500 ng/ml, in CKD patients with a TSAT ≤30%. [16]  Current guidelines recommend against use of iron products when ferritin is 500 ng/mL or greater.

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