Studies on the Production of Erythropoietin by Isolated Perfused Organs

Kuratowska, Z; Lewartowski, B; Michalak, Ewa

doi:10.1182/blood.v18.5.527.527

Cited by 115 publications

(16 citation statements)

References 12 publications

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“…The site of production of erythropoietin has not been unquestionably established. However, the predominant role of the kidneys seems to have been rendered very likely, especially after the perfusion experiments on isolated rabbit kidneys performed by Kuratowska et al (1961). Similar experiments have been performed by Fisher and Birdwell (1961) on dogs with the same results.…”

Section: Discussionsupporting

confidence: 63%

Erythrocytosis and Hypernephroma

Thorling¹,

Ersbak²

1964

Scandinavian Journal of Haematology

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The results of a study on the content of erythropoietic‐stimulating factor in the serum, urine and extracts from tumour tissue and normal renal tissue from a patient with erythrocytosis and hypernephroma of the left kidney are reported. Extracts from the solid parts of the tumour showed a high concentration of this factor. It seems reasonable to assume that this factor, which is presumed to be responsible for the patient's erythrocytosis, was produced by the tumour cells. Increased concentrations of erythropoietic‐stimulating factor were also revealed in the serum and urine after operation. Analyses of the metastases were not performed, but itseems reasonable to assume that these also produced an erythropoietic‐stimulating factor.

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Section: Discussionsupporting

confidence: 63%

Erythrocytosis and Hypernephroma

Thorling¹,

Ersbak²

1964

Scandinavian Journal of Haematology

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“…Subsequently, initial reports of low plasma Epo activity in anaemic patients with CKD appeared (32, 33). In 1961 Kuratowska et al (34) and Fisher and Birdwell (35) detected erythropoietic activity in the blood perfusate of isolated rabbit kidneys and in situ perfused dog kidneys, respectively. Nevertheless, for many years it was doubted that renal cells synthesise Epo directly because attempts failed to extract Epo from the kidney.…”

Section: The Identification Of the Epo‐producing Organsmentioning

confidence: 99%

Erythropoietin after a century of research: younger than ever

Jelkmann¹

2007

European J of Haematology

342

291

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In the light of the enthusiasm regarding the use of recombinant human erythropoietin (Epo) and its analogues for treatment of the anaemias of chronic renal failure and malignancies it is worth remembering that today's success has been based on a century of laborious research. The concept of the humoral regulation of haematopoiesis was first formulated in 1906. The term ‘erythropoietin’ for the erythropoiesis‐stimulating hormone was introduced in 1948. Native human Epo was isolated in 1977 and its gene cloned in 1985. During the last 15 yr, major progress has been made in identifying the molecules controlling Epo gene expression, primarily the hypoxia‐inducible transcription factors (HIF) that are regulated by specific O2 and oxoglutarate requiring Fe2+‐containing dioxygenases. With respect to the action of Epo, its dimeric receptor (Epo‐R) has been characterised and shown to signal through protein kinases, anti‐apoptotic proteins and transcription factors. The demonstration of Epo‐R in non‐haematopoietic tissues indicates that Epo is a pleiotropic viability and growth factor. The neuroprotective and cardioprotective potentials of Epo are reviewed with a focus on clinical research. In addition, studies utilising the Epo derivatives with prolonged half‐life, peptidic and non‐peptidic Epo mimetics, orally active drugs stimulating endogenous Epo production and Epo gene transfer are reviewed.

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“…The kidneys are the main EPO‐producing organs in humans , where peritubular interstitial cells govern its production , which is highly regulated. Baseline EPO levels can increase up to 1000‐fold in low blood oxygen content, for example in severe anaemia .…”

Section: Production and Metabolismmentioning

confidence: 99%

Erythropoietin doping in cycling: lack of evidence for efficacy and a negative risk–benefit

Heuberger

Tervaert

Schepers

et al. 2013

Brit J Clinical Pharma

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Imagine a medicine that is expected to have very limited effects based upon knowledge of its pharmacology and (patho)physiology and that is studied in the wrong population, with low-quality studies that use a surrogate end-point that relates to the clinical end-point in a partial manner at most. Such a medicine would surely not be recommended. The use of recombinant human erythropoietin (rHuEPO) to enhance performance in cycling is very common. A qualitative systematic review of the available literature was performed to examine the evidence for the ergogenic properties of this drug, which is normally used to treat anaemia in chronic renal failure patients. The results of this literature search show that there is no scientific basis from which to conclude that rHuEPO has performance-enhancing properties in elite cyclists. The reported studies have many shortcomings regarding translation of the results to professional cycling endurance performance. Additionally, the possibly harmful side-effects have not been adequately researched for this population but appear to be worrying, at least. The use of rHuEPO in cycling is rife but scientifically unsupported by evidence, and its use in sports is medical malpractice. What its use would have been, if the involved team physicians had been trained in clinical pharmacology and had investigated this properly, remains a matter of speculation. A single well-controlled trial in athletes in real-life circumstances would give a better indication of the real advantages and risk factors of rHuEPO use, but it would be an oversimplification to suggest that this would eradicate its use.

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Studies on the Production of Erythropoietin by Isolated Perfused Organs

Abstract: (1) Isolated organs of rabbits (kidney, liver, spleen and lungs) were perfused with rabbit blood. Experimental conditions of hypoxia and full oxygenation were applied. (2) It could be shown that under these conditions only the kidney produces the erythropoietic factor.

Cited by 115 publications

References 12 publications

Erythrocytosis and Hypernephroma

Erythrocytosis and Hypernephroma

Erythropoietin after a century of research: younger than ever

Erythropoietin doping in cycling: lack of evidence for efficacy and a negative risk–benefit

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