Key Takeaways

There is a high prevalence of iron deficiency in patients with chronic kidney disease (CKD).

Two types of iron deficiency are recognized:

  • Absolute iron deficiency which results from depletion of body iron stores.
  • Functional iron deficiency in which iron stores are present but not made available in sufficient quantities for erythropoiesis.

In patients with CKD:

  • Absolute iron deficiency results from increased blood loss, and to a lesser extent decreased iron intake and absorption.
  • Functional iron deficiency results from inflammation (increased hepcidin levels) and increased Fe demands (patients taking ESAs), though the latter may ultimately lead to depletion of body iron stores (i.e., absolute iron deficiency)

The diagnosis of iron deficiency typically involves use of serum ferritin and transferrin saturation levels. Bone marrow biopsy is the gold standard but is impractical and rarely indicated. Newer tests for diagnosing iron deficiency include percentage of hypochromic red blood cells (HRC) and reticulocyte Hb content.

Diagnosing iron deficiency in patients with CKD can be difficult. While both ferritin concentration and transferrin saturation decline in iron-deficiency anemia, the thresholds of ferritin and transferrin at which iron stores are deficient are higher in patients with CKD compared to those without CKD.

In patients with normal renal function, absolute iron deficiency is defined b serum ferritin levels <15-100 mcg/L (ng/mL) (depending on the presence of concomitant inflammation) and transferrin saturation (TSAT) <16%.

In patients with chronic kidney disease not on dialysis:

  • Absolute iron deficiency is defined as ferritin level <100 mcg/L (ng/mL) and transferrin saturation (TSAT) <20%.
  • Functional iron deficiency is defined as ferritin level >100 mcg/L (ng/mL) and TSAT <20%.

In patients with chronic kidney disease on dialysis:[efn-note]There is little evidence to support these higher thresholds in patients on dialysis[/efn_note]

  • Absolute iron deficiency is defined as ferritin level <200 mcg/L (ng/mL) and transferrin saturation (TSAT) <20%.
  • Functional iron deficiency is defined as ferritin level >200 mcg/L (ng/mL) and TSAT <20%.

Most CKD patients with serum ferritin levels >100 mcg/L (ng/mL) (>100 mcg/L [ng/mL]) have normal bone marrow iron stores (i.e. functional iron deficiency), yet many such patients will also have an increase in Hb concentration and/or reduction in ESA dose if supplemental iron is provided. It has been proposed that by overloading the reticuloendothelial system with iron, it is possible to promote mobilization and delivery of iron to developing erythrocytes.

Most clinical practice guidelines recommend treating CKD patients with iron to maintain a serum ferritin between 500 and 800 mcg/L (ng/mL).

While this approach may improve Hb and reduce ESA needs, it carries theoretical risks of infection and organ damage caused by iatrogenically elevated non–transferrin-bound iron and iron overload.

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