Iron status as measured by serum ferritin: The marker and its limitations

doi:10.1053/ajkd.1999.v34.aajkd0344b0012

American Journal of Kidney Diseases

Volume 34, Issue 4, Supplement, October 1999, Pages s12-s17

https://doi.org/10.1053/ajkd.1999.v34.aajkd0344b0012 Get rights and content

Abstract

Assessment of iron status is important, because iron deficiency and overload have pathologic consequences. Serum ferritin, the function of which is unknown, is frequently used to assess labile iron stores for the purpose of ensuring their adequacy for erythropoiesis. However, measurable ferritin levels can be increased when tissue ferritin is released during cellular injury, and erythropoietic blockade can increase the labile iron pool, elevating serum ferritin levels despite suppressed erythropoiesis. Erythropoietin-stimulated red blood cell (RBC) production can quickly decrease the labile cellular iron pool and reduce serum ferritin, unless supplemental iron is supplied. A serum ferritin level less than 12 μg/L indicates that there is no iron in the stores (absolute iron deficiency), and levels above 15 μg/L may still not be sufficient to meet erythropoietic demand. This is particularly true in patients receiving erythropoietin, in which the stimulated erythropoiesis requires extra iron supplies. Because of the limitations of serum ferritin measurements and questions regarding the effects of free iron, clinicians need not be too alarmed by high serum ferritin levels. At the very least, safety concerns must be balanced against the real need for iron supplementation to maintain adequate erythropoiesis. Am J Kidney Dis 34:s12-s17, 1999. Copyright © 1999 by National Kidney Foundation

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Cited by (63)

Narrative Review of Hyperferritinemia, Iron Deficiency, and the Challenges of Managing Anemia in Aboriginal and Torres Strait Islander Australians With CKD
2021, Kidney International Reports
Citation Excerpt :
There are no recommendations to vary targets according to ethnic groups. Low serum ferritin is a marker of iron deficiency.24,32,74,77,78 However, as an acute-phase protein, increased serum ferritin concentration, along with increases in other acute-phase reactants such as CRP, is observed in patients who have inflammation.35,67,79
Aboriginal and Torres Strait Islander Australians (Indigenous Australians) suffer some of the highest rates of chronic kidney disease (CKD) in the world. Among Indigenous Australians in remote areas of the Northern Territory, prevalence rates for renal replacement therapy (RRT) are up to 30 times higher than national prevalence. Anemia among patients with CKD is a common complication. Iron deficiency is one of the major causes. Iron deficiency is also one of the key causes of poor response to the mainstay of anemia therapy with erythropoiesis-stimulating agents (ESAs). Therefore, the effective management of anemia in people with CKD is largely dependent on effective identification and correction of iron deficiency. The current identification of iron deficiency in routine clinical practice is dependent on 2 surrogate markers of iron status: serum ferritin concentration and transferrin saturation (TSAT). However, questions exist regarding the use of serum ferritin concentration in people with CKD because it is an acute-phase reactant that can be raised in the context of acute and chronic inflammation. Serum ferritin concentration among Indigenous Australians receiving RRT is often markedly elevated and falls outside reference ranges within most national and international guidelines for iron therapy for people with CKD. This review explores published data on the challenges of managing anemia in Indigenous people with CKD and the need for future research on the efficacy and safety of treatment of anemia of CKD in patients with high ferritin and evidence iron deficiency.
Iron status at opposite ends of the menstrual function spectrum
2019, Journal of Trace Elements in Medicine and Biology
Although exercising women are at high risk of poor iron status, it is unknown how non-pathological, physiological menstrual function affects iron status. As such, this study investigates the association between menstrual function and iron status in exercising women with amenorrhea and exercising women with ovulatory, eumenorrheic menstrual cycles.
Cross-sectional analysis of iron depletion prevalence, iron status indices, exercise parameters, and diet composition.
Women aged 18–35 years performing at least 2 h per week of aerobic exercise were recruited. Women with amenorrhea (AMEN) were defined by the absence of menses for at least 90 days or less than 6 menses in the past 12 months (n = 82). Women with ovulatory, eumenorrheic menstrual cycles (OvEU) were defined by the presence of ovulatory cycles of 26-35 days in length for the past 6 months (n = 109). Group differences in serum ferritin (Ft), soluble transferrin receptor (sTfR), total body iron (TBI), hemoglobin (Hb), hematocrit (Hct), iron depletion prevalence (Ft <15 μg/L), peak oxygen consumption (VO_2peak), exercise minutes per week, and diet logs were assessed.
The prevalence of iron depletion was greater in OvEU when compared to AMEN (26% vs. 15%, p = 0.04). No significant differences were observed between AMEN and OvEU in Ft (30.2 ± 2.2 vs. 24.9 ± 2.6 μg/L; p = 0.62), sTfR (5.2 ± 1.4 vs. 4.9 ± 1.5 mg/L; p = 0.95), TBI (5.3 ± 2.7 vs. 4.8 ± 3.7 mg/kg; p = 0.42), Hb (13.2 ± 0.4 vs. 13.4 ± 0.6 g/dL; p = 0.80), Hct (39.5 ± 0.8% vs. 39.8 ± 4.1%; p = 0.93), or exercise parameters. AMEN consumed more vitamin C than OvEU (269 ± 180 vs. 129 ± 141 mg/day, p < 0.001), but all other dietary factors were similar between AMEN and OvEU.
Exercising women with ovulatory, eumenorrheic cycles are at a greater risk of iron depletion than exercising, amenorrheic women. Thus, menstrual function must be considered when screening for poor iron status in exercising women.
Thermodynamics of proton binding and weak (Cl-, Na+ and K+) species formation, and activity coefficients of 1,2-dimethyl-3-hydroxypyridin-4-one (deferiprone)
2014, Journal of Chemical Thermodynamics
Citation Excerpt :
Moreover deferiprone may be used in the detoxification of other metals, such as aluminium, plutonium, uranium, and in the treatment of copper overloading conditions (Wilson’s disease) [3,4,9]. Commercially deferiprone is known as Ferriprox ®, clinical studies have demonstrated that this drug is effective in promoting iron excretion and can lower serum ferritin [10] and iron stores in tissues of transfusion dependent thalassaemia patients (the precise mechanism is unknown). It is rapidly absorbed from the gastrointestinal tract and is eliminated via the kidneys, mainly in the form of glucuronide metabolite and iron-deferiprone complex.
The acid base properties of 1,2-dimethyl-3-hydroxypyridin-4-one (also known as deferiprone, def, figure 1), together with the solubility and the distribution ratio have been studied potentiometrically at different temperatures and ionic strengths in NaCl, KCl and in (CH₃)₄NCl aqueous solutions. The total solubility of deferiprone is fairly high (0.100 mol · dm⁻³ in pure water) and decreases with increasing salt concentration (salting out effect); this behaviour is greater in NaCl than in (CH₃)₄NCl aqueous solutions. From the analysis of the solubility and the distribution measurements it was possible to determine the Setschenow and the activity coefficients of the neutral species. Deferiprone shows two protonation steps, whose protonation constants are $\log K_{1}^{H} = 10.088$ and $\log K_{2}^{H} = 3.656$ at infinite dilution and T = 298.15 K. The ionic strength dependence of the protonation constants was interpreted both in terms of variation of the activity coefficients, using the Debye–Hückel, the SIT (Specific ion Interaction Theory) and the Pitzer approaches, or considering the formation of weak species with the ions of the supporting electrolyte (e.g. Na⁺, K⁺ and Cl⁻). Moreover, temperature gradients were provided for the two protonation constants. The stepwise protonation enthalpy values are negative in all cases (e.g. ΔH₁ = −19.2 kJ · mol⁻¹ and ΔH₂ = −13.8 kJ · mol⁻¹ at infinite dilution and T = 298.15 K) and become more negative increasing both temperature and ionic strength. It was observed that the proton binding process is mainly entropic in nature for the first protonation step and enthalpic for the second. The results are in good agreement with literature data.
Rethinking Iron Regulation and Assessment in Iron Deficiency, Anemia of Chronic Disease, and Obesity: Introducing Hepcidin
2012, Journal of the Academy of Nutrition and Dietetics
Citation Excerpt :
When ACD and ID/IDA coexist, ferritin levels may remain elevated secondary to the inflammatory process and can be misleading of actual cellular iron levels (see the Table) (42). Therefore, the sole use of serum ferritin to accurately assess iron status in individuals with chronic illness or inflammation is inadequate (43). However, coupling serum ferritin with the measurement of another acute phase reactant, such as C-reactive protein, can help to indicate if underlying inflammation exists and will help to explain elevated serum ferritin despite underlying ID (23).
Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed.
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2023, BMC Psychiatry
Comparison of serum iron status in healthy foals and foals with bronchopneumonia
2023, Pferdeheilkunde

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American Journal of Kidney Diseases

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References (0)

Cited by (63)

Narrative Review of Hyperferritinemia, Iron Deficiency, and the Challenges of Managing Anemia in Aboriginal and Torres Strait Islander Australians With CKD

Iron status at opposite ends of the menstrual function spectrum

Thermodynamics of proton binding and weak (Cl<sup>-</sup>, Na<sup>+</sup> and K<sup>+</sup>) species formation, and activity coefficients of 1,2-dimethyl-3-hydroxypyridin-4-one (deferiprone)

Rethinking Iron Regulation and Assessment in Iron Deficiency, Anemia of Chronic Disease, and Obesity: Introducing Hepcidin

Risk factors for osteoporosis in chronic schizophrenia on long-term treatment with antipsychotics: a cross-sectional study

Comparison of serum iron status in healthy foals and foals with bronchopneumonia