Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin

Ashby, Damien; Gale, Daniel P.; Busbridge, Mark; Murphy, Kevin G.; Duncan, Neill; Cairns, Tom; Taube, David; Bloom, Stephen R.; Tam, Frederick W.K.; Chapman, Richard; Maxwell, Patrick H.; Choi, P.

doi:10.3324/haematol.2009.013136

Cited by 170 publications

(152 citation statements)

References 25 publications

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“…This association was previously described in non-CKD patients and in dialysis patients (22)(23)(24)(25), and was also expected on the basis of recent findings on hepcidin as well as the involvement of EPO in iron metabolism (26). EPO reduces circulating hepcidin in humans (27) and directly affects the intestinal handling of iron in rat models (28). Inversely, absolute iron deficiency is associated with increased EPO levels and early blockage of erythroid differentiation (29).…”

Section: Discussionmentioning

confidence: 82%

Timing and Determinants of Erythropoietin Deficiency in Chronic Kidney Disease

Mercadal

Metzger

Casadevall

et al. 2012

Clinical Journal of the American Society of Nephrology

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on behalf of the NephroTest Study Group Summary Background and objectives Anemia in patients with CKD is highly related to impaired erythropoietin (EPO) response, the timing and determinants of which remain unknown.Design, setting, participants, & measurements This study measured EPO levels and studied their relation to GFR measured by 51Cr-EDTA renal clearance (mGFR) in 336 all-stage CKD patients not receiving any erythropoiesis-stimulating agent.Results In patients with anemia defined by World Health Organization criteria (hemoglobin [Hb] ,13 g/dl in men and 12 g/dl in women), EPO response to Hb level varied by mGFR level. EPO and Hb levels were negatively correlated (r=20.22, P=0.04) when mGFR was .30 ml/min per 1.73 m 2 , whereas they were not correlated when mGFR was ,30 (r=0.09, P=0.3; P for interaction=0.01). In patients with anemia, the ratio of observed EPO to the level predicted by the equation for their Hb level decreased from 0.72 (interquartile range, 0.57-0.95) for mGFR $60 ml/min per 1.73 m 2 to 0.36 (interquartile range, 0.16-0.69) for mGFR ,15. Obesity, diabetes with nephropathy other than diabetic glomerulopathy, absolute iron deficiency, and high C-reactive protein concentrations were associated with increased EPO levels, independent of Hb and mGFR.Conclusions Anemia in CKD is marked by an early relative EPO deficiency, but several factors besides Hb may persistently stimulate EPO synthesis. Although EPO deficiency is likely the main determinant of anemia in patients with advanced CKD, the presence of anemia in those with mGFR .30 ml/min per 1.73 m 2 calls for other explanatory factors.

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Section: Discussionmentioning

confidence: 82%

Timing and Determinants of Erythropoietin Deficiency in Chronic Kidney Disease

Mercadal

Metzger

Casadevall

et al. 2012

Clinical Journal of the American Society of Nephrology

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“…A single injection of Epo in human volunteers results in a rapid suppression of serum hepcidin. 90 In clinical trials in CKD patients either receiving hemodialysis or not, prolyl hydroxylase inhibitors which stabilize hypoxia-inducible factor and increase Epo production were effective in lowering hepcidin and correcting hemoglobin even without intravenous (IV) iron supplementation. 91,92 However, the use of ESAs in patients with chronic kidney disease or cancer has been associated with serious adverse effects.…”

Section: E Fung Et Almentioning

confidence: 99%

Manipulation of the hepcidin pathway for therapeutic purposes

2013

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“…Some methods use an internal standard, either hepcidin analogs or bioactive hepcidin-25 synthesized with stable isotopes. [3][4][5][6][7][8][9][10] Recently, immunochemical (IC) assays for hepcidin-25 have also been developed, which comprise of competitive radioimmunoassays (RIA) 11 and enzyme-linked immunosorbent assays (ELISA). 12,13 Currently there is no reference method for hepcidin measurements.…”

Section: Introductionmentioning

confidence: 99%