Related Experiment Video
Updated: May 2, 2026
Measurement of Tissue Non-Heme Iron Content using a Bathophenanthroline-Based Colorimetric Assay
Published on: January 31, 2022
A 3-marker index improves the identification of iron disorders in CKD anaemia
Lucile Mercadal1, Marie Metzger2, Jean Philippe Haymann3
1Institut National de la Santé et de la Recherche Médicale U1018, CESP Centre for research in Epidemiology and Population Health, Epidemiology of Diabetes, Obesity, and Kidney Diseases Team, Villejuif, France ; Department of Nephrology, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
Insights
A new 3-marker index accurately classifies iron disorders in chronic kidney disease (CKD) anemia. This index highlights hypotransferrinemia and functional iron deficiency as key issues, especially in advanced CKD.
Area of Science:
- Nephrology
- Hematology
- Clinical Chemistry
Background:
- Iron disorders are prevalent and intricate in chronic kidney disease (CKD).
- Accurate classification of these disorders is crucial for effective anemia management in CKD patients.
Purpose of the Study:
- To evaluate a novel 3-marker index for improved classification of iron disorders in CKD-related anemia.
- To assess the association between hemoglobin (Hb) levels and various iron deficiency profiles.
Main Methods:
- A cohort of 1011 non-dialysis CKD outpatients were analyzed.
- Iron indexes were calculated using serum ferritin, transferrin saturation (TSAT), and total iron-binding capacity (TIBC).
- Glomerular filtration rates (mGFR) and hepcidin levels were measured in subsets of patients.
Main Results:
- The TSAT-TIBC-ferritin index demonstrated superior performance in explaining Hb variations compared to 2-marker indexes.
- Hypotransferrinemia (20%) and non-inflammatory functional iron deficiency (19%) were identified as the most common iron disorders.
- Lower Hb levels were observed across all abnormal iron profiles, with a more pronounced decrease in patients with mGFR < 30 mL/min/1.73 m(2).
Conclusions:
- The 3-marker index effectively identifies hypotransferrinemia and non-inflammatory functional iron deficiency as primary contributors to iron disorders in CKD anemia.
- These specific iron profiles are linked to significant Hb reduction, particularly in advanced CKD (mGFR < 30 mL/min/1.73 m(2)).
- Incorporating this index may aid in patient stratification for clinical trials and optimize iron therapy management in CKD.
Background:
Iron disorders are common and complex in chronic kidney disease (CKD). We sought to determine whether a 3-marker index would improve the classification of iron disorders in CKD anaemia.
Methods:
We studied the association between Hb level and iron indexes combining 2 or 3 of the following markers: serum ferritin (<40 ng/mL), transferrin saturation (TSAT<20%) and total iron binding capacity (TIBC<50 µmol/L) in 1011 outpatients with non-dialysis CKD participating in the Nephrotest study. All had glomerular filtration rates measured (mGFR) by (51)Cr-EDTA renal clearance; 199 also had hepcidin measures.
Results:
The TSAT-TIBC-ferritin index explained Hb variation better than indexes combining TSAT-TIBC or ferritin-TSAT. It showed hypotransferrinaemia and non-inflammatory functional iron deficiency (ID) to be more common than either absolute or inflammatory ID: 20%, 19%, 6%, and 2%, respectively. Hb was lower in all abnormal, compared with normal, iron profiles, and decreased more when mGFR was below 30 mL/min/1.73 m(2) (interaction p<0.0001). In patients with mGFR<30 mL/min/1.73 m(2), the Hb decreases associated with hypotransferrinaemia, non-inflammatory functional ID, and absolute ID were 0.83±0.16 g/dL, 0.51±0.18 and 0.89±0.29, respectively. Compared with normal iron profiles, hepcidin was severely depressed in absolute ID but higher in hypotransferrinaemia.
Conclusions:
The combined TSAT-TIBC-ferritin index identifies hypotransferrinaemia and non-inflammatory functional ID as the major mechanisms of iron disorders in CKD anaemia. Both disorders were associated with a greater decrease in Hb when mGFR was <30 mL/min/1.73 m(2). Taking these iron profiles into account may be useful in stratifying patients in clinical trials of CKD anaemia and might improve the management of iron therapy.
Related Concept Videos
01:28Chronic Kidney Disease III: Interprofessional Care
01:24Chronic Kidney Disease II: Clinical Manifestations
01:25Chronic Kidney Disease I: Introduction
01:18Effects of EDTA on End-Point Detection Methods
In the visual method, metal-ion indicators (metallochromic dyes), which have distinct colors in their free and complex forms, are added to the mixture to signal the titration's end point. They form stable complexes with metal ions, but these complexes are weaker than the corresponding metal–EDTA complexes. As a...
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...