Ferritin and TSAT Normal Ranges in CKD
In CKD patients, absolute iron deficiency is defined as TSAT ≤20% with ferritin <100 μg/L in predialysis and peritoneal dialysis patients, or <200 μg/L in hemodialysis patients, while functional iron deficiency occurs when TSAT ≤20% despite ferritin >100 μg/L (or >200 μg/L in hemodialysis), primarily driven by hepcidin-mediated iron sequestration from chronic inflammation. 1
Iron Parameter Thresholds by CKD Stage
Non-Dialysis and Peritoneal Dialysis CKD Patients
- Absolute iron deficiency: TSAT ≤20% AND ferritin ≤100 μg/L 1, 2
- Functional iron deficiency: TSAT ≤20% AND ferritin >100 μg/L 1, 2
- Target maintenance levels: TSAT ≥20% and ferritin ≥100 μg/L 1
Hemodialysis Patients
- Absolute iron deficiency: TSAT ≤20% AND ferritin ≤200 μg/L 1, 2
- Functional iron deficiency: TSAT ≤20% AND ferritin >200 μg/L 1
- Upper safety limits: Avoid chronically maintaining TSAT >50% or ferritin >800 μg/L 1
- Proactive iron therapy threshold: Consider IV iron when ferritin <700 μg/L and TSAT ≤40% 1
The Critical Role of Hepcidin in CKD Iron Metabolism
Hepcidin's Mechanism in Iron Sequestration
Hepcidin is a liver-produced hormone that blocks iron absorption from the gut and prevents iron release from body stores, creating functional iron deficiency even when total body iron is adequate. 1
- Chronic inflammation in CKD stimulates hepatic hepcidin production 1, 3, 4
- Elevated hepcidin levels prevent intestinal iron absorption, making oral iron largely ineffective in dialysis patients 5
- Hepcidin blocks iron recycling through the reticuloendothelial system, trapping iron in macrophages where it cannot be used for erythropoiesis 5
- Hepcidin levels increase progressively from CKD stage 3 through 5 4
Hepcidin and Iron Status Interactions
- In absolute iron deficiency (TSAT <20%, ferritin <40-100 μg/L), hepcidin is appropriately downregulated 4
- In functional iron deficiency and iron-replete states, hepcidin remains elevated due to inflammation and reduced renal clearance 3, 4
- Hepcidin correlates positively with ferritin (P <0.0001) and TSAT (P = 0.0217) 4
- Hepcidin correlates negatively with erythropoietin levels (P = 0.0258) 4
Clinical Implications of Hepcidin
Hepcidin has not proved to be a consistent marker to distinguish absolute from functional iron deficiency or determine ESA responsiveness in CKD patients, limiting its current clinical utility. 1
- A hepcidin cutoff ≤34 ng/mL may differentiate absolute iron deficiency from other categories (AUC = 0.836, P <0.0001) 4
- Elevated hepcidin predicts the need for parenteral iron therapy and higher ESA doses to overcome iron-restricted erythropoiesis 4
- Functional iron deficiency patients show significantly higher hepcidin and high-sensitivity CRP levels compared to absolute iron deficiency 3
Important Clinical Caveats
Limitations of Current Iron Parameters
The presently used parameters (ferritin and TSAT) are not reliable for estimating body iron stores or predicting response to therapy, particularly in the setting of chronic inflammation. 1
- Ferritin is an acute phase reactant and may be falsely elevated in inflammatory states 6, 7
- TSAT and ferritin lack diagnostic value above normal ranges in dialysis patients 5
- These parameters cannot distinguish between inflammation-driven functional iron deficiency (hepcidin-mediated sequestration) versus kinetic iron deficiency from ESA-stimulated erythropoiesis 1
Prevalence of Iron Deficiency in CKD
- 15-72.8% of non-dialysis CKD patients have either ferritin <100 μg/L or TSAT <20% 1, 6
- 8-20% have both parameters below threshold 1
- In hemodialysis patients, 36.3% have TSAT <20%, 60.2% have ferritin <100 μg/L, and 28.0% have both 1
Monitoring Frequency
- Measure TSAT and ferritin at least every 3 months in hemodialysis patients to optimize erythropoiesis by adjusting IV iron dosing 1
- Annual monitoring minimum for non-dialysis CKD patients 7