Assessing Iron Status: Beyond Serum Ferritin and Transferrin Saturation
Abstract
The increasing prevalence of multiple comorbidities among anemic patients with chronic kidney disease has made the use of serum ferritin and transferrin saturation more challenging in diagnosing iron deficiency. Because serum ferritin is an acute-phase reactant and because the inflammatory state may inhibit the mobilization of iron from reticuloendothelial stores, the scenario of patients with serum ferritin >800 ng/ml, suggesting iron overload, and transferrin saturation <20%, suggesting iron deficiency, has become more common. This article revisits the basis for the Kidney Disease Outcomes Quality Initiative recommendations regarding the use of serum ferritin and transferrin saturation in guiding iron therapy, then explores some of the newer alternative markers for iron status that may be useful when serum ferritin and transferrin saturation are insufficient. These newer tests include reticulocyte hemoglobin content, percentage of hypochromic red cells, and soluble transferrin receptor, all of which have shown some promise in limited studies. Finally, the role of hepcidin, a hepatic polypeptide, in the pathophysiology of iron mobilization is reviewed briefly.
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Three genetic variants (rs1800562 and rs1799945 in HFE and rs855791 in TMPRSS6) associate with increased serum iron, ferritin, and transferrin saturation and decreased transferrin levels, serving as instruments for systemic iron status.
“3 genetic variants (rs1800562 and rs1799945 in the hemochromatosis gene [HFE] and rs855791 in the transmembrane protease serine 6 gene [TMPRSS6]) that associate with increased serum iron, ferritin, and transferrin saturation and decreased transferrin levels, thus serving as instruments for systemic iron status.”
From Associations of genetically determined iron status across the phenome: A mendelian randomization study (2019) · cites this paper as [15]
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- Authors
- Wish, J. B.
- Affiliations
- University Hospitals of Cleveland (US)
- Corresponding author
- Wish, Jay B.
- ORCID
- Wish, Jay B.
- Venue
- Clinical Journal of the American Society of Nephrology
- Published
- 2006-09
- Volume
- 1
- Issue
- Supplement_1
- Pages
- S4-S8
- ISSN
- 1555-9041 (ISSN-L)
- OpenAlex
- W2166218331
- Cited by
- 556
- References
- 1
- Citations by year
- 2026: 18 · 2025: 10 · 2024: 22 · 2023: 33 · 2022: 49 · 2021: 50 · 2020: 39 · 2019: 39 · 2018: 40 · 2017: 37 · 2016: 24 · 2015: 27 · 2014: 29 · 2013: 28 · 2012: 25
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Journal of the American Society of Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- iron status assessment, iron deficiency, chronic kidney disease, anemia, serum ferritin, transferrin saturation, inflammatory status, iron overload, reticulocyte hemoglobin content, soluble transferrin receptor, hepcidin, iron mobilization, KDOQI guidelines, iron therapy
- MeSH terms
- Erythrocytes, Ferritins, Hematinics, Renal Dialysis, Hemoglobins, Humans, Infusions, Intravenous, Iron, Predictive Value of Tests, Quality of Health Care, Receptors, Transferrin, Reticulocytes, Sensitivity and Specificity, Transferrin, Biomarkers, Practice Guidelines as Topic, Patient Selection, Anemia, Iron-Deficiency, Antimicrobial Cationic Peptides, Renal Insufficiency, Chronic, Iron Compounds, Hepcidins
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