Does chronic kidney disease cause iron deficiency in adult patients, particularly those on dialysis?

Does CKD Cause Iron Deficiency?

Yes, chronic kidney disease directly causes iron deficiency through multiple mechanisms, making it one of the most common complications of CKD, particularly in dialysis patients. 1

Mechanisms by Which CKD Causes Iron Deficiency

CKD causes iron deficiency through several distinct pathways that work simultaneously:

Direct Blood Loss Mechanisms

• Hemodialysis patients lose approximately 400 mg of iron every 3 months from blood remaining in dialysis tubing and dialyzers, frequent phlebotomy for laboratory testing, and procedural losses 1
• Pediatric hemodialysis patients experience cumulative annual iron losses of approximately 1.6 g/1.73 m² body surface area, compared to 0.9 g/1.73 m² in predialysis patients 1
• Gastrointestinal blood losses occur at higher rates in CKD patients, with mean daily losses of 11 mL/m² in pediatric hemodialysis patients versus 6 mL/m² in predialysis patients 1

Impaired Iron Absorption and Mobilization

• Renal failure itself directly impairs iron absorption from the gastrointestinal tract, independent of other factors 1
• Chronic inflammation in CKD increases hepcidin production by the liver, which blocks intestinal iron absorption and prevents mobilization of iron from reticuloendothelial stores 1, 2, 3
• Hemodialysis patients have demonstrably lower intestinal iron absorption compared to healthy individuals 3

Reduced Intake and Increased Demand

• CKD patients often have reduced dietary iron intake due to uremia-related anorexia and dietary restrictions 1
• Erythropoietin therapy dramatically increases iron demand—approximately 600 mg of iron is needed just to support red blood cell production when raising hematocrit from 25% to 35% 1

Prevalence and Clinical Significance

More than 50% of U.S. ESRD patients receiving erythropoietin are iron deficient, which directly contributes to persistent anemia and its associated morbidity and mortality 1, 4

Iron deficiency in CKD exists in two forms:

• Absolute iron deficiency: Depleted iron stores with transferrin saturation ≤20% and ferritin ≤100 μg/L (predialysis/peritoneal dialysis) or ≤200 μg/L (hemodialysis) 1, 4
• Functional iron deficiency: Adequate total body iron stores but insufficient iron availability for erythropoiesis due to hepcidin-mediated sequestration, characterized by transferrin saturation ≤20% with elevated ferritin 1, 4, 2

Critical Diagnostic Pitfalls

Standard ferritin cutoffs used in non-CKD patients (<12-45 ng/mL) do not apply in CKD because chronic inflammation elevates ferritin independent of actual iron stores 5, 6. The inflammatory state in renal failure makes ferritin an unreliable marker when interpreted using normal reference ranges 5.

Impact on Outcomes

Anemia from iron deficiency in CKD is associated with increased morbidity, mortality, and reduced quality of life, with the severity of anemia correlating with worse outcomes 5, 7, 4. Iron replacement therapy improves survival, decreases morbidity, and increases quality of life in this population 5.

Treatment Implications

Oral iron supplementation cannot compensate for the iron losses in hemodialysis patients because gastrointestinal absorption is insufficient to match the combined losses from dialysis, phlebotomy, and GI bleeding 1. Intravenous iron is required for dialysis patients and is preferred when oral iron fails in predialysis patients 1, 5.

The majority of CKD patients with confirmed iron deficiency warrant gastrointestinal investigation to exclude treatable causes of blood loss, provided they are fit for procedures, and this decision should be made in conjunction with nephrology 1, 5.