What constitutes a diagnosis of iron deficiency in a patient with chronic kidney disease (CKD) stage 2 and a history of iron deficiency anemia?

Iron Deficiency Diagnosis in CKD Stage 2

In a patient with CKD stage 2 (non-dialysis dependent), iron deficiency is diagnosed when transferrin saturation (TSAT) is ≤20% AND serum ferritin is ≤100 ng/mL. 1, 2

Diagnostic Criteria by CKD Status

The definition of iron deficiency varies significantly based on dialysis status, which is critical to understand:

For Non-Dialysis CKD Patients (Including CKD Stage 2)

• Absolute iron deficiency is defined as TSAT ≤20% AND ferritin ≤100 ng/mL 1, 2, 3
• This threshold is lower than for dialysis patients because ferritin acts as an acute-phase reactant and is elevated in dialysis patients independent of true iron stores 1

For Hemodialysis Patients (For Comparison)

• Absolute iron deficiency is defined as TSAT ≤20% AND ferritin ≤200 ng/mL 1, 3
• The higher ferritin threshold accounts for chronic inflammation in dialysis patients 1

For Peritoneal Dialysis Patients

• Same criteria as non-dialysis patients: TSAT ≤20% AND ferritin ≤100 ng/mL 1, 3

Functional vs. Absolute Iron Deficiency

Understanding this distinction is essential for proper diagnosis and treatment:

• Absolute iron deficiency occurs when iron stores are truly depleted (TSAT ≤20% with ferritin ≤100 ng/mL in non-dialysis CKD) 1, 3
• Functional iron deficiency (iron-restricted erythropoiesis) occurs when TSAT ≤20% but ferritin is elevated (>100 ng/mL), indicating adequate stores but insufficient iron availability for erythropoiesis 3, 4
• Functional iron deficiency results from inflammation-driven hepcidin upregulation, which traps iron in macrophages and prevents its mobilization for red blood cell production 2, 4

Required Laboratory Assessment

To properly diagnose iron deficiency in CKD stage 2, obtain:

• Complete iron panel including calculated TSAT (serum iron alone is insufficient) 2
• Serum ferritin as a surrogate marker for tissue iron stores 1
• Transferrin saturation representing iron available to bone marrow for erythropoiesis 1
• Complete blood count to assess hemoglobin, mean corpuscular volume (MCV), and other cell lines 1
• Reticulocyte count with reticulocyte index to assess bone marrow response appropriateness 2, 5

Critical Pitfalls to Avoid

Ferritin Interpretation in CKD

• Ferritin is an acute-phase reactant and can be falsely elevated by inflammation, infection, or malignancy even when true iron stores are depleted 1
• In non-dialysis CKD patients with inflammation, consider measuring C-reactive protein to assess whether elevated ferritin reflects inflammation rather than adequate iron stores 1
• TSAT may be more reliable than ferritin alone in CKD patients because it is less affected by inflammation 1

When to Suspect GI Blood Loss

• In non-dialysis CKD patients not on erythropoietic-stimulating agents and without significant menstrual losses, finding iron deficiency should prompt careful assessment for gastrointestinal bleeding 1
• The majority of CKD patients with confirmed iron deficiency anemia warrant GI investigation if they are fit enough for these procedures 1

Multiple Contributing Factors

• Iron deficiency is only one contributor to anemia in CKD; other mechanisms include erythropoietin deficiency, hemolysis, inflammation, and bone marrow suppression 1, 4
• Abnormalities in two or more cell lines (white blood cells, hemoglobin, platelets) warrant hematology consultation as this may indicate more complex bone marrow pathology 1, 5

Clinical Context for CKD Stage 2

• CKD becomes a potential cause of anemia when GFR falls below 60 mL/min/1.73m² 1
• Iron deficiency is present in 25-37.5% of patients presenting with anemia of CKD 2
• The causes of iron deficiency in CKD are multifactorial: reduced intake, reduced absorption, GI blood loss, and inflammation-mediated iron sequestration 1, 4