Serum iron markers are inadequate for guiding iron repletion in chronic kidney disease.

BACKGROUND AND OBJECTIVES: Iron (Fe) overload may complicate parenteral Fe therapy used to enhance the efficacy of erythropoietic-stimulating agents in the treatment of anemia of chronic kidney disease. However, serum Fe markers are influenced by inflammation or malignancy and may not accurately reflect the amount of body Fe. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied the relationship between parenteral Fe therapy, conventional serum Fe markers, and liver iron concentration (LIC) measured using magnetic resonance R2 relaxometry (FerriScan) in 25 Fe-deficient predialysis chronic kidney disease patients before and 2 and 12 weeks after single high-dose intravenous Fe and in 15 chronic hemodialysis patients with elevated serum ferritin (>500 µg/L). RESULTS: In predialysis patients, there was strong dose dependency between the administered Fe dose and changes in LIC at weeks 2 and 12; however, no dose dependency between Fe dose and changes in ferritin or transferrin saturation (TSAT) were observed. In hemodialysis patients, LIC correlated with the cumulative Fe dose and duration of dialysis but not with current ferritin or TSAT. The cumulative Fe dose remained a significant independent predictor of LIC in a multiple regression model. Two dialysis patients who received >6 g parenteral Fe had substantially elevated LIC >130 µmol/g, which is associated with hemochromatosis. CONCLUSIONS: In Fe-deficient predialysis patients, intravenous Fe therapy is associated with increases in LIC unrelated to changes in conventional Fe markers. In hemodialysis patients, TSAT and ferritin are poor indicators of body Fe load, and some patients have LICs similar to those found in hemochromatosis.

Measurement and mapping of liver iron concentrations using magnetic resonance imaging.

Measurement of liver iron concentration (LIC) is an important clinical procedure in the management of transfusional iron overload with iron chelation. LIC gives an indication of over- or underchelation. Although chemical assay of needle biopsy samples from the liver has been considered the "gold standard" of LIC measurement, needle biopsy sampling errors can be surprisingly large owing to the natural spatial variation of LIC throughout the liver and the small size of biopsy specimens. A magnetic resonance imaging technique has now been developed that enables safe noninvasive measurement and imaging of LIC with a known accuracy and precision. Measurements of LIC can be made over the range of LIC encountered in clinical practice. The technique is based on the measurement and imaging of proton transverse relaxation rates (R2) within the liver. The R2 imaging technique can be implemented on most clinical 1.5-T MRI instruments, making it readily available to the clinical community.

Arterial embolization hyperthermia: hepatic iron particle distribution and its potential determination by magnetic resonance imaging.

Arterial embolization hyperthermia (AEH) consists of arterially embolizing liver tumours with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. A critical component of AEH is the concentration and distribution of ferromagnetic particles in the normal hepatic parenchyma (NHP), as well as in the tumour tissue. If the distribution of particles in NHP is heterogeneous, with areas of high concentration, then unwanted areas of necrosis may result during AEH. Using an in vivo rabbit liver tumour model, this study showed that hepatic arterial infusion of ferromagnetic particles does indeed result in a heterogeneous distribution of iron in NHP. The radiological technique of magnetic resonance imaging (MRI) was then evaluated as a potential tool for non-invasively and prospectively determining the concentration and distribution of particles within the hepatic tumour and NHP following hepatic arterial infusion. A preliminary in vitro experiment showed that although the concentration of iron within the tumour tissue (1.92-3.50 mg of iron per gram of tissue) was too great to measure, MRI was able to accurately determine the lower iron concentration (0.10-0.53 mg of iron per gram of tissue) in NHP. Further work is needed to evaluate MRI under in vivo conditions. If successful, MRI could become an important component of an emerging novel treatment for advanced hepatic malignancies.