Hepcidin in Anemia and Inflammation in Chronic Kidney Disease

Małyszko, Jolanta; Myśliwiec, M

doi:10.1159/000098522

Cited by 86 publications

(87 citation statements)

References 192 publications

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“…Several studies have reported that IV iron has greater efficacy with rhuEpo than oral iron, perhaps as a result of reduced iron absorption from the gut and poor patient compliance with oral medication (4)(5)(6)(7)(8)18). although new formulations of iV iron have drastically reduced the risk of immediate adverse effects, a variety of long-term consequences of iV iron have been reported in the literature (15,19). Furthermore, several studies have demonstrated that the administration of iV iron releases free iron, which may react with hydrogen peroxide to produce hydroxyl radical oxidants and may lead to increased oxidative stress that can potentially damage cellular lipids, nucleic acids, proteins and carbohydrates (20,21).…”

Section: Discussionmentioning

confidence: 99%

“…iV iron bypasses the physiologic controls of iron absorption and storage, thereby exposing the patient to higher levels of circulating free iron and higher tissue levels of iron. a number of authors recently reviewed the link between free or stored iron and a variety of disease states, including cardiovascular disease (18,22), carcinogenesis (19,23) and infection (15,24). the chemical and microbiological quality of water used in dialysate plays a crucial role in the mortality and morbidity of patients on hd.…”

Section: Discussionmentioning

confidence: 99%

“…hepcidin, a serum protein, is produced by the liver and is a key regulator of iron mobilization. In HD patients, bacterial contamination of the dialysate leads to increased inflammatory cytokine production and chronic inflammation (14,15). Therefore, we hypothesized that sterile dialysate may improve the effect of oral iron supplementation on erythropoiesis.…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness of oral iron to manage anemia in long-term hemodialysis patients with the use of ultrapure dialysate

Tsuchida¹,

Paudyal²,

Paudyal

et al. 2010

Experimental and Therapeutic Medicine

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Abstract. the aim of this study was to evaluate the effectiveness of oral iron to manage anemia in long-term hemodialysis (hd) patients using ultrapure dialysate. this study was prospectively conducted on 23 patients (11 males and 12 females; median age 60 years, range 35-81) who underwent hd in our hospital from march to September 2007. the patients were randomly assigned to two treatment groups. The first group of 11 patients received ferrous fumarate 305 mg per oral tablet once a day, while the second group of 12 patients received infusions of 50 mg iron in a 0.9% sodium chloride solution. at the end of the 6-month treatment, patients receiving oral iron and intravenous iron had a significant increase in transferrin saturation from baseline (20.1±8.9 to 29.7±7.2; p=0.011 and 17.4±6.1 to 33.7±8.6; p=0.0001, respectively) and ferritin (32.6±15.4 to 115.4±28.2; p=0.0001 and 57.8±26.7 to 183.5±47.5; p=0.0002, respectively). in both groups, hemoglobin, hematocrit and dry weight were increased, but did not reach statistical significance. Moreover, both groups showed a significant reduction in the mean weekly erythropoietin dose from baseline (5,590.9±1,513.6 to 3,727.3±1,618.1; p=0.011 and 6,775.8±2,292.2 to 4,375.0±2,473.7; p=0.027, respectively). Oral iron is indeed as effective as intravenous iron in managing anemia in hd patients using ultrapure dialysate.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effectiveness of oral iron to manage anemia in long-term hemodialysis patients with the use of ultrapure dialysate

Tsuchida¹,

Paudyal²,

Paudyal

et al. 2010

Experimental and Therapeutic Medicine

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“…The hepcidin immunoassay utilized in this study has been shown to detect inflammation, iron deficiency and hereditary hemochromatosis. 6 Hepcidin has been proposed as a potential marker of iron bioavailability for erythropoiesis in chronic kidney disease 8 and also for identifying coexisting iron deficiency in patients with concomitant anemia of chronic disease, [39][40][41] and has been proposed as an alternative to the sTfR-F index for discriminating between iron deficiency and anemia of chronic disease. 42 A comparative study of different assays for hepcidin analysis found that although the absolute value for results at each laboratory differed significantly, results for samples correlated well and analytical variance was generally low.…”

Section: S-r Pasricha Et Almentioning

confidence: 99%

Serum hepcidin as a diagnostic test of iron deficiency in premenopausal female blood donors

Pasricha¹,

McQuilten²,

Westerman³

et al. 2011

Haematologica

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BackgroundCurrently used indicators of iron status have limitations. Hepcidin, a key regulator of iron metabolism, is reduced in iron deficiency. We sought to determine the properties of hepcidin as a diagnostic test of iron deficiency. Design and MethodsSera from female, non-anemic, whole blood donors were analyzed for hepcidin (enzymelinked immunosorbent assay), ferritin, soluble transferrin receptor and C-reactive protein. Iron deficiency was defined as (i) serum ferritin less than 15 ng/mL or (ii) soluble transferrin receptor /log(ferritin) index greater than 3.2 if the C-reactive protein concentration was less than 10 mg/L, or greater than 2.2 if the C-reactive protein concentration was greater than 10 mg/L). Receiver operating characteristic curves were plotted to determine the overall utility and identify optimal cut-points of hepcidin as a test of iron deficiency. ResultsIn 261 blood donors the prevalence of iron deficiency defined by ferritin concentration was 59/261 [22.6% (17.5, 27.7)], whereas defined by soluble transferrin receptor/log(ferritin) index it was 53/261 [20. 4% (15.4, 25.2)]. The 95% reference range of hepcidin concentration in the iron-replete population was 8.2-199.7 ng/mL. The area under the receiver operating characteristic curve for hepcidin compared with ferritin concentration less than 15 ng/mL was 0.87 (0.82, 0.92), while that compared with the soluble transferrin receptor /log(ferritin) index was 0.89 (95% CI 0.84, 0.93). For a diagnosis of iron deficiency defined by the soluble transferrin receptor/log(ferritin) index, hepcidin less than 8 ng/mL had a sensitivity of 41.5% and a specificity of 97.6%, while hepcidin less than 18 ng/mL had a sensitivity of 79.2% and a specificity of 85.6%. ConclusionsSerum hepcidin concentration may be a useful indicator of deficient iron stores. Further studies are required to evaluate the role of hepcidin in the diagnosis of iron deficiency in other groups of patients.

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“…In cases such as these, persistently high levels of hepatic hepcidin expression, probably due to chronic inflammatory state, may explain why duodenal iron absorption remains inadequately low and the iron sequestration within cells of the reticuloendothelial system is high (19). In view of the relationship between hepcidin and the iron transporters Ferroportin and DMT1, an experimental model studying these proteins will serve to elucidate modifications in renal pathways in anemia associated with chronic kidney diseases.…”

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confidence: 99%

Role of the kidney in iron homeostasis: renal expression of Prohepcidin, Ferroportin, and DMT1 in anemic mice

Veuthey

D'Anna²,

Roque³

2008

American Journal of Physiology-Renal Physiology

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It is known that renal tissue plays a role in normal iron homeostasis. The current study examines kidney function in iron metabolism under hemolytic anemia studying renal expression of Prohepcidin, Ferroportin (MTP1), and divalent metal transporter 1 (DMT1). The relationship between these proteins and iron pigments was also investigated. Immunohistochemical procedures to study renal expression of Prohepcidin, MTP1, and DMT1 were performed in healthy and anemic mice. Renal tissue iron was determined by Prussian blue iron staining. To assess anemia evolution and erythropoietic recovery, we used conventional tests. In healthy mice, Prohepcidin expression was marked in proximal tubules and inner medulla and absent in outer medulla. Cortical tissue of healthy mice also showed MTP1 immunostaining, mainly in the S2 segment of proximal tubules. Medullar tissue showed MTP1 expression in the inner zone. In addition, S2 segments showed intense DMT1 immunoreactivity with homogeneous DMT1 distribution throughout renal medulla. The main cortical findings in hemolytic anemia were in S2 segments of proximal tubules where we found that decreased Prohepcidin expression coincided with an increment in Ferroportin and DMT1 expression. This expression pattern was concomitant with increased iron in the same tubular zone. However, in medullar tissue both Prohepcidin and MTP1 decreased and DMT1 was detected mainly in larger diameter tubules. Our findings clearly demonstrate that in hemolytic anemia, renal Prohepcidin acts in coordination with renal Ferroportin and DMT1, indicating the key involvement of kidney in iron homeostasis when iron demand is high. Further research is required to learn more about these regulatory mechanisms.

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Hepcidin in Anemia and Inflammation in Chronic Kidney Disease

Cited by 86 publications

References 192 publications

Effectiveness of oral iron to manage anemia in long-term hemodialysis patients with the use of ultrapure dialysate

Effectiveness of oral iron to manage anemia in long-term hemodialysis patients with the use of ultrapure dialysate

Serum hepcidin as a diagnostic test of iron deficiency in premenopausal female blood donors

Role of the kidney in iron homeostasis: renal expression of Prohepcidin, Ferroportin, and DMT1 in anemic mice

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