Pharmacokinetics of ferric bepectate-a new intravenous iron drug for treating iron deficiency.

IV iron is indicated in clinical conditions, where rapid anaemia alleviation and repletion of iron stores are required. The acute toxicity of IV iron is ascribed to the presence of labile iron in plasma. Thus, shorter plasma residence time might improve the safety profile, even for compounds holding-on the iron tightly. In this single-centre, open-label, single-dose escalation study, we evaluated the elimination kinetics of ferric bepectate (FBP) compared to those of ferric carboxymaltose (FCM). Thirty-three iron-depleted anaemic patients who had undergone cardiac surgery were included and received 200, 500 or 1500 mg FBP or 500 mg FCM. Plasma drug curves were subjected to model-free analysis. Because saturation kinetics was found, a compartmental model with limited elimination capacity was applied. Urinary iron excretion was also analysed. The initial non-compartmental analysis revealed an increasing AUC/dose ratio for FBP. For both drugs, the central distribution compartment corresponded to plasma volume, and elimination followed Michaelis-Menten saturation kinetics. Maximal elimination rates (Vmax ) were 224 mg/h and 81 mg/h for FBP 500 mg and FCM 500 mg, respectively; drug concentrations at half Vmax (Km ), 99 mg/L and 212 mg/L, respectively; and terminal plasma half-life (T½), 3.05 h and 8.96 h, respectively. Both drugs were equally effective in eliciting an early ferritin rise. Urinary iron excretion was measurable in all patients receiving FCM but not in those receiving FBP, which was well tolerated. Intravenous iron drugs are subject to capacity-limited elimination with different saturation thresholds. Urinary iron excretion can be used as a surrogate for labile plasma iron.

Aggregation-Induced Emission Probe for Specific Turn-On Quantification of Soluble Transferrin Receptor: An Important Disease Marker for Iron Deficiency Anemia and Kidney Diseases.

Transferrin receptor (TfR) is overexpressed on the surface of many cancer cells due to its vital roles in iron circulation and cellular respiration. Soluble transferrin receptor (sTfR), a truncated extracellular form of TfR in serum, is an important marker of iron deficiency anemia (IDA) and bone marrow failure in cancer patients. More recently, sTfR level in urine has been related to a specific kidney disease of Henoch-Schönlein purpura nephritis (HSPN). Despite the universal significance of sTfR, there is still a lack of a simple and sensitive method for the quantification of sTfR. Furthermore, it is desirable to have a probe that can detect both TfR and sTfR for further comparison study. In this work, we developed a water-soluble AIE-peptide conjugate with aggregation-induced emission (AIE) characteristics. Taking advantage of the negligible emission from molecularly dissolved tetraphenylethene (TPE), probe TPE-2T7 was used for the light-up detection of sTfR. The probe itself is nonemissive in aqueous solution, but it turns on its fluorescence upon interaction with sTfR to yield a detection limit of 0.27 µg/mL, which is much lower than the sTfR level in IDA patients. Furthermore, a proof-of-concept experiment validates the potential of the probe for diagnosis of HSPN by urine test.

Excessive fluoride consumption increases haematological alteration in subjects with iron deficiency, thalassaemia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

Excessive fluoride consumption leads to accelerated red blood cell death and anaemia. Whether that increases the haematological alteration in subjects with haematological disorders (iron deficiency, thalassaemia, and G-6-PD deficiency) is still unclear. The fluoride in serum and urine and haematological parameters of students at Mae Tuen School (fluoride endemic area) were analysed and compared to those of students at Baan Yang Poa and Baan Mai Schools (control areas). Iron deficiency, thalassaemia, and G-6-PD deficiency were also diagnosed in these students. The students at Mae Tuen School had significantly (P < 0.001) higher levels of mean fluoride in the serum and urine than those in control areas. In both control and fluoride endemic areas, students with haematological disorders had significantly lower levels of Hb, Hct, MCV, MCH, and MCHC than those without haematological disorders. Moreover, the lowest levels of Hb, MCH, and MCHC were observed in the students with haematological disorders who live in the fluoride endemic area. Thus, the excessive fluoride consumption increased haematological alteration in subjects with iron deficiency, thalassaemia, and G-6-PD deficiency and that may increase the risk of anaemia in these subjects.

Modulation of urinary siderophores by the diet, gut microbiota and inflammation in mice.

Mammalian siderophores are believed to play a critical role in maintaining iron homeostasis. However, the properties and functions of mammalian siderophores have not been fully clarified. In this study, we have employed Chrome Azurol S (CAS) assay which is a well-established method for bacterial siderophores study, to detect and quantify mammalian siderophores in urine samples. Our study demonstrates that siderophores in urine can be altered by diet, gut microbiota and inflammation. C57BL/6 mice, fed on plant-based chow diets which contain numerous phytochemicals, have more siderophores in the urine compared to those fed on purified diets. Urinary siderophores were up-regulated in iron overload conditions, but not altered by other tested nutrients status. Further, germ-free mice displayed 50% reduced urinary siderophores, in comparison to conventional mice, indicating microbiota biotransformation is critical in generating or stimulating host metabolism to create more siderophores. Altered urinary siderophores levels during inflammation suggest that host health conditions influence systemic siderophores level. This is the first report to measure urinary siderophores as a whole, describing how siderophores levels are modulated under different physiological conditions. We believe that our study opens up a new field in mammalian siderophores research and the technique we used in a novel manner has the potential to be applied to clinical purpose.

Hepcidin on 24-hour urine collection: preanalytical aspects and correlation with ferritin levels.

BACKGROUND: Urine hepcidin measurement is a potential non-invasive tool for assessing iron stores. However, hepcidin, due to its amphipathic structure, tends to aggregate and to adhere to surfaces in a protein-poor environment. In this study, we assessed the effect of solid bovine serum albumin (BSA) at different final concentrations (0, 2.5 or 5 g/L) in limiting the loss of hepcidin in spot urine samples. We also explored how hepcidin measured on plasma, spot or 24-hour urine collections can identify iron deficiency. METHODS: Hepcidin levels were quantified on plasma, spot (with or without BSA) or 24-h urine collections for 33 volunteers. Hematological and iron status parameters were measured for each individual. The ability to detect iron deficiency (defined as a ferritin level <30 µg/L) based on plasma, spot or 24-h urine collections hepcidin levels was assessed by the means of receiver operator curves analysis. RESULTS: The addition of BSA into urine prior to sample collection prevented hepcidin loss by 13.3% (mean) in spot urine samples whatever the amount. The areas under the receiver operator curves obtained for detecting iron deficiency were respectively 0.94 and 0.93 for hepcidin levels obtained on plasma and 24-h urine collections. CONCLUSION: In this study, we showed that the addition of solid BSA into urine sample collection containers could prevent aggregation of hepcidin and that 24-h urine hepcidin levels could be as efficient as plasma concentrations for identifying iron deficiency.

Urinary Kidney Injury Molecules in Children with Iron-Deficiency Anemia.

BACKGROUND: The aim of this study was to investigate the urine levels of human kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-ß-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with iron-deficiency anemia (IDA). MATERIAL AND METHODS: Thirty-five children with IDA and 32 matched healthy controls were recruited. We assessed complete blood count, serum iron, iron-binding capacity, ferritin, serum levels of urea, creatinine (Cr), sodium (Na), potassium (K), calcium (Ca), and glucose levels. Estimated glomerular filtration rate (eGFR) was calculated. Urinary NAG, NGAL, KIM-1, and L-FABP were measured and divided by urine creatinine for comparisons. RESULTS: There were no significant differences in serum urea, Cr, or eGFR between the IDA group and the control group (p>0.05, for all). IDA patients had significantly higher urine NGAL/Cr, L-FABP/Cr, KIM-1/Cr, and NAG/Cr compared with the control group (p<0.05). There were significant negative correlations between hemoglobin, hematocrit, red blood cell count, and urine NGAL/Cr, NAG/Cr, L-FABP/Cr, KIM-1/Cr levels (p<0.05). CONCLUSIONS: Higher urinary kidney injury molecule levels in IDA patients suggest a possible subclinical renal injury in pediatric IDA patients whose renal functions and serum electrolytes were normal.

Urinary Hepcidin Levels in Iron-Deficient and Iron-Supplemented Piglets Correlate with Hepcidin Hepatic mRNA and Serum Levels and with Body Iron Status.

Among livestock, domestic pig (Sus scrofa) is a species, in which iron metabolism has been most intensively examined during last decade. The obvious reason for studying the regulation of iron homeostasis especially in young pigs is neonatal iron deficiency anemia commonly occurring in these animals. Moreover, supplementation of essentially all commercially reared piglets with iron entails a need for monitoring the efficacy of this routine practice followed in the swine industry for several decades. Since the discovery of hepcidin many studies confirmed its role as key regulator of iron metabolism and pointed out the assessment of its concentrations in biological fluids as diagnostic tool for iron-related disorder. Here we demonstrate that urine hepcidin-25 levels measured by a combination of weak cation exchange chromatography and time-of-flight mass spectrometry (WCX-TOF MS) are highly correlated with mRNA hepcidin expression in the liver and plasma hepcidin-25 concentrations in anemic and iron-supplemented 28-day old piglets. We also found a high correlation between urine hepcidin level and hepatic non-heme iron content. Our results show that similarly to previously described transgenic mouse models of iron disorders, young pigs constitute a convenient animal model to explore accuracy and relationship between indicators for assessing systemic iron status.

Bone remodelling is reduced by recovery from iron-deficiency anaemia in premenopausal women.

Iron-deficiency anaemia (IDA), one of the most common and widespread health disorders worldwide, affects fundamental metabolic functions and has been associated with deleterious effects on bone. Our aim was to know whether there are differences in bone remodelling between a group of premenopausal IDA women and a healthy group, and whether recovery of iron status has an effect on bone turnover markers. Thirty-five IDA women and 38 healthy women (control group) were recruited throughout the year. IDA women received pharmacological iron treatment. Iron biomarkers, aminoterminal telopeptide of collagen I (NTx), procollagen type 1 N-terminal propeptide (P1NP), 25-hydroxyvitamin D, and parathormone (PTH) were determined at baseline for both groups and after treatment with pharmacological iron for the IDA group. IDA subjects were classified as recovered (R) or non-recovered (nR) from IDA after treatment. NTx levels were significantly higher (p <0.001), and P1NP levels tended to be lower in IDA women than controls after adjusting for age and body mass index (BMI), with no differences in 25-hydroxyvitamin D or PTH. After treatment, the R group had significantly lower NTx and P1NP levels compared to baseline (p <0.05 and p <0.001 respectively), whilst no significant changes were seen in the nR group. No changes were seen in 25-hydroxyvitamin D or PTH for either group. IDA is related to higher bone resorption independent of age and BMI. Recovery from IDA has a concomitant beneficial effect on bone remodelling in premenopausal women, decreasing both bone resorption and formation.

Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women.

Fibroblast growth factor 23 (FGF23) is an osteocyte-derived hormone that regulates phosphate and vitamin D homeostasis. Through unknown mechanisms, certain intravenous iron preparations induce acute, reversible increases in circulating FGF23 levels that lower serum phosphate in association with inappropriately low levels of calcitriol, similar to genetic diseases of primary FGF23 excess. In contrast, studies in wild-type mice suggest that iron deficiency stimulates fgf23 transcription but does not result in hypophosphatemia because FGF23 is cleaved within osteocytes by an unknown catabolic system. We tested the association of iron deficiency anemia with C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels in 55 women with a history of heavy uterine bleeding, and assessed the longitudinal biochemical response over 35 days to equivalent doses of randomly-assigned, intravenous elemental iron in the form of ferric carboxymaltose (FCM) or iron dextran. Iron deficiency was associated with markedly elevated cFGF23 (807.8 ± 123.9 relative units [RU]/mL) but normal iFGF23 (28.5 ± 1.1 pg/mL) levels at baseline. Within 24 hours of iron administration, cFGF23 levels fell by approximately 80% in both groups. In contrast, iFGF23 transiently increased in the FCM group alone, and was followed by a transient, asymptomatic reduction in serum phosphate <2.0 mg/dL in 10 women in the FCM group compared to none in the iron dextran group. Reduced serum phosphate was accompanied by increased urinary fractional excretion of phosphate, decreased calcitriol levels, and increased parathyroid hormone levels. These findings suggest that iron deficiency increases cFGF23 levels, and that certain iron preparations temporarily increase iFGF23 levels. We propose that intravenous iron lowers cFGF23 in humans by reducing fgf23 transcription as it does in mice, whereas carbohydrate moieties in certain iron preparations may simultaneously inhibit FGF23 degradation in osteocytes leading to transient increases in iFGF23 and reduced serum phosphate.

Urinary hepcidin level as an early predictor of iron deficiency in children: A case control study.

BACKGROUND: The ideal screening test would be capable of identifying iron deficiency in the absence of anemia. We tried to detect role of urinary hepcidin-25 level in early prediction of iron deficiency in children. METHODS: This is a case control study performed on 100 children in Hematology Unit of Pediatric Department, Zagazig University Hospital, Egypt. Our study included 25 cases of iron deficiency (ID) stage-1 (iron depletion), 25 cases ID stage-2 (iron-deficient erythropoiesis), 25 cases ID stage-3 (iron deficiency anemia) and 25 healthy children as a control group. Estimation of iron status parameters was done. Urinary hepcidin-25 level was detected. RESULTS: Urinary hepcidin-25 level was significantly lower in all stages of iron deficiency than in control group, more significant reduction in its level was observed with the progress in severity of iron deficiency. Urinary hepcidin showed significant positive correlation with hemoglobin, mean corpuscular volume, hematocrit value, serum iron and ferritin and transferrin saturation. In contrary, it showed significant negative correlation with serum transferrin and total iron binding capacity.Urinary hepcidin at cutoff point ≤0.94 nmol/mmol Cr could Predict ID stage-1 with sensitivity 88% and specificity 88%. Cutoff point ≤0.42 nmol/mmol Cr could predict ID stage-2 with sensitivity 96% and specificity 92%. Cutoff point ≤0.08 nmol/mmol Cr could Predict ID stage-3 with Sensitivity 96% and specificity 100%. CONCLUSIONS: We can conclude that detection of urinary hepcidin-25 level was a simple and non invasive test and could predict iron deficiency very early, before appearance of hematological affections.

The relationship between body iron stores and blood and urine cadmium concentrations in US never-smoking, non-pregnant women aged 20-49 years.

BACKGROUND: Cadmium is a ubiquitous environmental pollutant associated with increased risk of leading causes of mortality and morbidity in women, including breast cancer and osteoporosis. Iron deficiency increases absorption of dietary cadmium, rendering women, who tend to have lower iron stores than men, more susceptible to cadmium uptake. We used body iron, a measure that incorporates both serum ferritin and soluble transferrin receptor, as recommended by the World Health Organization, to evaluate the relationships between iron status and urine and blood cadmium. METHODS: Serum ferritin, soluble transferrin receptor, urine and blood cadmium values in never-smoking, non-pregnant, non-lactating, non-menopausal women aged 20-49 years (n=599) were obtained from the 2003-2008 National Health and Nutrition Examination Surveys. Body iron was calculated from serum ferritin and soluble transferrin receptor, and iron deficiency defined as body iron <0 mg/kg. Robust linear regression was used to evaluate the relationships between body iron and blood and urine cadmium, adjusted for age, race, poverty, body mass index, and parity. RESULTS: Per incremental (mg/kg) increase in body iron, urine cadmium decreased by 0.003 µg/g creatinine and blood cadmium decreased by 0.014 µg/L. Iron deficiency was associated with 0.044 µg/g creatinine greater urine cadmium (95% CI=0.020, 0.069) and 0.162 µg/L greater blood cadmium (95% CI=0.132, 0.193). CONCLUSIONS: Iron deficiency is a risk factor for increased blood and urine cadmium among never-smoking, pre-menopausal, non-pregnant US women, independent of age, race, poverty, body mass index and parity. Expanding programs to detect and correct iron deficiency among non-pregnant women merits consideration as a potential means to reduce the risk of cadmium associated diseases.

A novel TMPRSS6 mutation that prevents protease auto-activation causes IRIDA.

IRIDA (iron-refractory iron-deficiency anaemia) is a rare autosomal-recessive disorder hallmarked by hypochromic microcytic anaemia, low transferrin saturation and high levels of the iron-regulated hormone hepcidin. The disease is caused by mutations in the transmembrane serine protease TMPRSS6 (transmembrane protease serine 6) that prevent inactivation of HJV (haemojuvelin), an activator of hepcidin transcription. In the present paper, we describe a patient with IRIDA who carries a novel mutation (Y141C) in the SEA domain of the TMPRSS6 gene. Functional characterization of the TMPRSS6(Y141C) mutant protein in cultured cells showed that it localizes to similar subcellular compartments as wild-type TMPRSS6 and binds HJV, but fails to auto-catalytically activate itself. As a consequence, hepcidin mRNA expression is increased, causing the clinical symptoms observed in this IRIDA patient. The present study provides important mechanistic insight into how TMPRSS6 is activated.

Proinflammatory state, hepcidin, and anemia in older persons.

In patients with overt inflammatory diseases, up-regulated hepcidin impairs iron absorption and macrophage release, causing anemia. Whether the mild proinflammatory state of aging is associated with increased hepcidin is unknown. We characterized the relationships between urinary hepcidin, iron status, anemia, and inflammation in 582 patients 65 years or older participating in the InCHIANTI (Invecchiare in Chianti, "Aging in the Chianti Area") study, a population-based study of aging in Tuscany, Italy. Compared with nonanemic persons, urinary hepcidin (nanograms/milligram of urinary creatinine) was significantly lower in iron deficiency and inflammation anemia compared with no anemia or other anemia types. Urinary hepcidin was positively correlated with log(ferritin) and negatively correlated with the soluble transferrin receptor/log(ferritin) ratio but not correlated with markers of inflammation: interleukin-6 (IL-6), IL-1beta, tumor necrosis factor-alpha, and C-reactive protein (CRP). Lower iron was significantly correlated with higher IL-6 and CRP. Adjusting for confounders, IL-6 and CRP remained significantly associated with serum iron, with no evidence that such a relationship was accounted for by variability in urinary hepcidin. In conclusion, elevated proinflammatory markers were associated with anemia and low iron status, but not with higher urinary hepcidin. Future studies should test whether hepcidin production becomes up-regulated only in situations of overt inflammation.

[Hepcidin and Plasmodium falciparum malaria in anemic school children in Mali]. / Hepcidine et infection due a Plasmodium falciparum chez un groupe d'ecoliers anémiés du Mali.

Hepcidin is a peptide produced by hepatocytes and detectable in blood and urine. Urinary hepcidin excretion appeared to be significantly increasing in humans with acute and chronic infections or inflammatory diseases. However, the effects of common tropical parasitic infections on hepcidin have not been sufficiently examined. We carried out a study in school children from Mali living in a neighborhood where Plasmodium falciparum malaria and Schistosoma haematobium infections are prevalent. Anemia (hemoglobin < 120 g/l) prevalence was very high among these children (68%); 24% had iron deficiency anemia. The prevalence of infections was also high (65% had at least one infection and 41% had C-reactive protein (CRP) levels > 10 mg/L). S. haematobium was diagnosed in 64%. We assessed first morning urine hepcidin excretion in a sub-sample of 15 children with either S. haematobium, P. falciparum malaria or none; 14 of these 15 children were included in the analyses. Children with P. falciparum malaria excreted significantly higher levels of hepcidin than those with S. haematobium (chi2 = 3.86; p = 0.05) or without any infection (chi2 = 5.95; p = 0.01). Urinary hepcidin correlated significantly with CRP (Spearman's r = 0.59; p = 0.001) and serum ferritin (Spearman's r = 0.73; p = 0.003). Our study confirms the still limited evidence of an association between human malaria and increased urinary hepcidin and points out the need for further studies to define the contribution of hepcidin to anemia associated with this disease.

An insight into the relationships between hepcidin, anemia, infections and inflammatory cytokines in pediatric refugees: a cross-sectional study.

BACKGROUND: Hepcidin, a key regulator of iron homeostasis, is increased in response to inflammation and some infections, but the in vivo role of hepcidin, particularly in children with iron deficiency anemia (IDA) is unclear. We investigated the relationships between hepcidin, cytokines and iron status in a pediatric population with a high prevalence of both anemia and co-morbid infections. METHODOLOGY/PRINCIPAL FINDINGS: African refugee children <16 years were consecutively recruited at the initial post-resettlement health check with 181 children meeting inclusion criteria. Data on hematological parameters, cytokine levels and co-morbid infections (Helicobacter pylori, helminth and malaria) were obtained and urinary hepcidin assays performed. The primary outcome measure was urinary hepcidin levels in children with and without iron deficiency (ID) and/or ID anaemia (IDA). The secondary outcome measures included were the relationship between co-morbid infections and (i) ID and IDA, (ii) urinary hepcidin levels and (iii) cytokine levels. IDA was present in 25/181 (13.8%). Children with IDA had significantly lower hepcidin levels (IDA median hepcidin 0.14 nmol/mmol Cr (interquartile range 0.05-0.061) versus non-IDA 2.96 nmol/mmol Cr, (IQR 0.95-6.72), p<0.001). Hemoglobin, log-ferritin, iron, mean cell volume (MCV) and transferrin saturation were positively associated with log-hepcidin levels (log-ferritin beta coefficient (beta): 1.30, 95% CI 1.02 to 1.57) and transferrin was inversely associated (beta: -0.12, 95% CI -0.15 to -0.08). Cytokine levels (including IL-6) and co-morbid infections were not associated with IDA or hepcidin levels. CONCLUSIONS/SIGNIFICANCE: This is the largest pediatric study of the in vivo associations between hepcidin, iron status and cytokines. Gastro-intestinal infections (H. pylori and helminths) did not elevate urinary hepcidin or IL-6 levels in refugee children, nor were they associated with IDA. Longitudinal and mechanistic studies of IDA will further elucidate the role of hepcidin in paediatric iron regulation.

Hepcidin and iron status among pregnant women in Bangladesh.

Although hepcidin, a recently discovered peptide hormone, is considered a major regulator of iron metabolism and anemia in chronic inflammation, its role in anemia during pregnancy has not been characterized. Our objective was to characterize the role of hepcidin in anemia during pregnancy. We examined the relationships between urinary hepcidin, iron status indicators, hemoglobin, erythropoietin, alpha-1 acid glycoprotein, and C-reactive protein in a cross-sectional study conducted among 149 pregnant rural Bangladeshi women with biospecimens obtained during home visits. Urinary hepcidin was measured using surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry. Urinary hepcidin, as log(intensity per mmol/L creatinine), was correlated with log ferritin (r = 0.33, p <0.001), the transferrin receptor index (r = -0.22, p = 0.007), and log alpha-1 acid glycoprotein (r = 0.20, p = 0.01), but not hemoglobin (r = 0.07, p= 0.40), log transferrin receptor (r = -0.07, p = 0.41), log erythropoietin (r = -0.01, p = 0.88) or log C-reactive protein (r = 0.06, p = 0.48). The strength of the relationship between hepcidin and ferritin was maintained in multiple linear regression analyses after enhancing the sample with data from women selected for low iron stores (n = 41). Among pregnant women in a community-based study in rural Bangladesh, urinary hepcidin levels were related to iron status and AGP but not hemoglobin, erythropoietin, or C-reactive protein.

Immunoassay for human serum hepcidin.

We developed and validated the first serum enzyme-linked immunosorbent assay for hepcidin, the principal iron-regulatory hormone that has been very difficult to measure. In healthy volunteers, the 5% to 95% range of hepcidin concentrations was 29 to 254 ng/mL in men (n = 65) and 17 to 286 ng/mL in women (n = 49), with median concentrations 112 versus 65 (P < .001). The lower limit of detection was 5 ng/mL. Serum hepcidin concentrations in 24 healthy subjects correlated well with their urinary hepcidin (r = 0.82). Serum hepcidin appropriately correlated with serum ferritin (r = 0.63), reflecting the regulation of both proteins by iron stores. Healthy volunteers showed a diurnal increase of serum hepcidin at noon and 8 pm compared with 8 am, and a transient rise of serum hepcidin in response to iron ingestion. Expected alterations in hepcidin levels were observed in a variety of clinical conditions associated with iron disturbances. Serum hepcidin concentrations were undetectable or low in patients with iron deficiency anemia (ferritin < 10 ng/mL), iron-depleted HFE hemochromatosis, and juvenile hemochromatosis. Serum hepcidin concentrations were high in patients with inflammation (C-reactive protein > 10 mg/dL), multiple myeloma, or chronic kidney disease. The new serum hepcidin enzyme-linked immunosorbent assay yields accurate and reproducible measurements that appropriately reflect physiologic, pathologic, and genetic influences, and is informative about the etiology of iron disorders.