Serum hepcidin concentration in chronic haemodialysis patients: associations and effects of dialysis, iron and erythropoietin therapy

Weiss, Günter; Theurl, Igor; Eder, Susanne; Koppelstaetter, Christian; Kurz, Katharina; Sonnweber, Thomas; Kobold, Uwe; Mayer, Gert

doi:10.1111/j.1365-2362.2009.02182.x

Cited by 99 publications

(116 citation statements)

References 47 publications

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“…The original SELDI-TOF assay described by Tomosugi et al (30) found hepcidin levels to be elevated in hemodialysis patients compared with normal healthy controls. This has been confirmed by various other groups (9,11,17,22,23,27,37,42,44,45), although the absolute values of hepcidin vary up to 10-fold depending on the assay used. Thus, most assays suggest a normal range for plasma hepcidin to be in the range of 1 to 55 ng/ml, whereas values from hemodialysis patients are in the range of 27 to 158 ng/ml ( Table 1).…”

Section: Hepcidin Measurement In Ckd Patientssupporting

confidence: 66%

Current Status of the Measurement of Blood Hepcidin Levels in Chronic Kidney Disease

Macdougall¹,

Małyszko²,

Hider³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Hepcidin is a small defensin-like peptide produced in the liver in response to anemia, hypoxia, or inflammation. In addition to its anti-microbial properties, it has also been found to be a key regulator of iron utilization, providing increased understanding of why chronic kidney disease patients absorb iron poorly from the gut and also why many hemodialysis patients develop functional iron deficiency in the presence of inflammation. Hepcidin synthesis is upregulated in uremia, as in other inflammatory states. The ability to measure hepcidin in biologic fluids has stimulated interest in the potential applicability of this measurement as a more informative marker of iron status than the traditional iron indices such as serum ferritin and transferrin saturation. Until recently, however, the assays for measuring hepcidin have lacked precision, accuracy, and internal validation. Over the last few years, however, several assays have become available that address these limitations. Broadly speaking, these can be divided into radioimmunoassays, ELISAs, and mass spectrometry methods. The purpose of this review is to outline the various assays available at the present time, to critique their advantages and limitations, and to report comparative data in patients with chronic kidney disease. A concern with the immunoassays is that they detect more than biologically active hepcidin-25. Mass spectrometric assays are specific for hepcidin-25 but are labor intensive and require more costly and sophisticated instrumentation. Thus, although mass spectrometry is more accurate, it is less practical for routine clinical use at the present time.

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Section: Hepcidin Measurement In Ckd Patientssupporting

confidence: 66%

Current Status of the Measurement of Blood Hepcidin Levels in Chronic Kidney Disease

Macdougall¹,

Małyszko²,

Hider³

et al. 2010

Clinical Journal of the American Society of Nephrology

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“…This increase is partly counteracted by active clearance of this small hormone peptide during the dialytic procedure [11 -13]. The clearance of hepcidin is likely to be substantially influenced by the type of hemodialysis technique [12,13], but this remains an area of further active research. Nevertheless, the majority of studies available until the beginning of this year have reported increased pre-dialytic serum hepcidin levels in CHD patients as compared to controls [10 -12, 14 -20].…”

Section: Hepcidin As a Player In The Anemia Of Chdmentioning

confidence: 99%

Hepcidin levels in chronic hemodialysis patients: a critical evaluation

Valenti

Pelusi

Campostrini

et al. 2014

Clinical Chemistry and Laboratory Medicine

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Altered systemic iron metabolism is a key element of uremia, and functional iron deficiency mainly related to subclinical inflammation makes it difficult to maintain proper control of anemia in chronic hemodialysis patients (CHD). In the last decade, the hepatic hormone hepcidin has been progressively recognized as the master regulator of circulating iron levels through the modulation of cellular iron fluxes in response to iron stores, as well as to erythroid and inflammatory stimuli. Hepcidin is cleared by the kidney and progression of renal disease has been associated to increased serum hepcidin levels. This, in turn, reduces iron availability for erythropoiesis, suggesting anti-hepcidin strategies for improving anemia control. Moreover, hepcidin has been recently implicated in the pathogenesis of long-term complications of dialysis, like accelerated atherosclerosis. Initial studies almost invariably reported a sustained increase of serum hepcidin in chronic hemodialysis patients. Noteworthy, such studies included relatively few patients and controls that were poorly matched for major determinants of serum hepcidin at population level, i.e., age and gender. More recent data based on accurately matched larger series challenge the view that hepcidin is intrinsically increased in hemodialysis patients, showing a marked inter-and intra-individual variability of hormone levels. Here we take a critical look to the data published so far on hepcidin levels in CHD, analyze the reasons underlying the discrepancies in available studies and the hepcidin variability in CHD, and point out the need for further studies in large series of well-characterized CHD patients and controls.

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“…33 Hepcidin is also downregulated by hypoxia, and recent studies reveal that AI patients who respond to high-dose EPO therapy have concomitant decreases in hepcidin. 34 However, it remains to be determined whether hypoxia-inducible factor 1␣, the body's primary hypoxia sensor, directly suppresses hepcidin synthesis.…”

Section: Anemia Of Inflammationmentioning

confidence: 99%

Anemia in Elderly Patients: An Emerging Problem for the 21st Century

Vanasse

Berliner

2010

Hematology

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Anemia is a significant problem in elderly patients. Although many anemic elderly patients can be diagnosed with nutritional deficiency, anemia of chronic inflammation or comorbid diseases that explain their decreased hematocrit, the etiology of anemia in a significant fraction remains obscure. There is evidence to suggest that the hematopoietic stem cell displays increasing erythropoietin (EPO) resistance with age. EPO levels rise in elderly, nonanemic patients, and it is hypothesized that there is an interplay between this rising demand for EPO and the decreasing ability of the aging kidney to produce adequate hormone to meet that need. There is further considerable evidence that aging is associated with increased proinflammatory cytokine expression and that many of these cytokines can contribute to EPO insensitivity. Consequently, genetic variation in the expression of these proinflammatory cytokines may influence the development of anemia in elderly patients, both through induction of hepcidin expression (anemia of inflammation) and through cytokine suppression of erythroid colony formation. The impact of inflammatory mediators, EPO insensitivity, and other factors that may act on the hematopoietic stem cell to decrease erythropoiesis are under active study and should serve to elucidate the pathophysiology of this important cause of morbidity and mortality in elderly individuals. A better understanding of the pathophysiology of anemia in elderly patients should provide critical entry points for interventions that will improve survival and quality of life in the aging population.Anemia of any degree is recognized as a significant independent contributor to morbidity, mortality, and frailty in elderly patients. 1,2 Although anemia has often been considered a normal consequence of aging, the pathophysiology of such an age-related decline in erythrocyte production is obscure, and efforts to understand anemia in elderly individuals have become a major target of research interest. Recent studies suggest that, although anemia likely arises in part from the cumulative effect of age-related comorbidities and physical decline, there are still age-specific changes in the hematopoietic system that influence red blood cell production. Understanding of these changes could have important diagnostic and therapeutic implications for addressing this common problem. Because the number of elderly individuals is expected to reach unprecedented levels in the 21 st century, anemia represents an emerging global health problem negatively impacting quality of life in a significant proportion of the elderly population and requiring an ever-greater allocation of health care resources. Epidemiology of Anemia in Elderly PatientsIn the Third National Health and Nutrition Examination Survey (NHANES III) study, the incidence of anemia in men and women older than age 65 was 11% and 10%, respectively. 3 The prevalence of anemia rose rapidly after the age of 50, approaching a rate greater than 20% in those individuals aged 85 years or older. I...

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Serum hepcidin concentration in chronic haemodialysis patients: associations and effects of dialysis, iron and erythropoietin therapy

Cited by 99 publications

References 47 publications

Current Status of the Measurement of Blood Hepcidin Levels in Chronic Kidney Disease

Current Status of the Measurement of Blood Hepcidin Levels in Chronic Kidney Disease

Hepcidin levels in chronic hemodialysis patients: a critical evaluation

Anemia in Elderly Patients: An Emerging Problem for the 21st Century

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