Effect of Human Erythropoietin Derived From Recombinant Dna on the Anaemia of Patients Maintained by Chronic Haemodialysis

Winearls, C. G.; Pippard, MartinJ; Downing, MichaelR; Oliver, David K.; Reid, C. D. L.; Cotes, P. Mary

doi:10.1016/s0140-6736(86)92192-6

Cited by 1,075 publications

(395 citation statements)

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“…The application of exogenous recombinant human EPO has been shown to accelerate the recovery of red cell volume in phlebotomized animals 12 as well as in autologous blood donors. 13 Its use in healthy persons, however, is still hampered by the facts that not all side effects of the recombinant hormone may yet be known and that the reported side effects 44,45 are not completely understood in regard to their causal mechanisms. If these concerns are overcome with increased experience in the treatment of chronic anemia with recombinant human EPO, its use may acquire a place in preoperative autologous blood donation.…”

Section: Discussionmentioning

confidence: 99%

Serial immunoreactive erythropoietin levels in autologous blood donors

Lorentz¹,

Jendrissek²,

Eckardt

et al. 1991

Transfusion

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The variations in plasma erythropoietin (EPO) concentration during preoperative deposit of autologous blood were studied in 12 patients (8 men, 4 women). Four donations were scheduled at weekly intervals. A predonation hemoglobin concentration of 11 g per dL (110 g/L) was required. Hemoglobin concentration decreased from 14.3 ± 1.1 g per dL (143 ± 11 g/L) (mean ± SD) before the first donation to 11.7 ± 0.7 g per dL (117 ± 7 g/L) on Day 22 (p<0.0001). Reticulocyte counts increased from a median of 31,800 (range, 4900-95,000) per \xL (median, 32 x 10 9 /L [range, 5-95 x 10 9 /L]) to 93,800 (16,800-194,900) per \iL (median, 94 x 10 9 /L [range, 17-195 x 10 9 /L]) on Day 28 (p<0.01). Plasma EPO concentration was 17.8 ± 5.1 mU per mL prior to the first donation and displayed a small and transient peak after each donation. A sustained elevation followed each peak. Although plasma EPO concentration differed significantly from the baseline value after the first donation, only the peak concentrations after the second (35.5 ± 15.5 mU/mL), third (38.0 ± 14.5 mU/ mL), and fourth (36.1 ±11.0 mU/mL) donations exceeded the normal range. The moderate, biphasic increase in plasma EPO concentration and the moderate increase in erythropoiesis suggest two strategies in autologous blood donation that should be investigated with respect to efficiency and safety: 1) more aggressive donation schemes, which reduce donation intervals and/or the minimum hemoglobin concentration and 2) the administration of recombinant human EPO. TRANSFUSION 1991;31:650-654. Abbreviations: EPO = erythropoietin.THE IMMUNOLOGIC AND INFECTIOUS risks of transfusion 1,2 can be minimized by the use of autologous blood. Preoperative autologous blood donation considerably reduces homologous transfusion requirements in surgery. 3 " 8 Frozen storage of red cells allows the preoperative deposit of a large number of blood units, but it is costly and time-consuming. On the other hand, liquid storage is limited to 5 weeks for whole blood and 7 weeks for packed red cells. 9,10 The efficiency of preoperative deposit in the liquid state thus depends on the rate of recovery from blood loss, that is, on the degree of stimulation of erythropoiesis.Erythropoietin (EPO) is the primary humoral regulator of erythropoiesis. 11 Increasing the availability of EPO may therefore enhance the efficiency of preoperative donation programs. This increased availability of EPO may be achieved by allowing the modulation of donation schemes (shorter donation intervals, lower minimum

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Section: Discussionmentioning

confidence: 99%

Serial immunoreactive erythropoietin levels in autologous blood donors

Lorentz¹,

Jendrissek²,

Eckardt

et al. 1991

Transfusion

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“…It is highly effective at correcting the anaemia, restoring energy levels, and increasing patient well being and quality of life (Winearls et al, 1986;Eschbach et al, 1987Eschbach et al, , 1989Evans et al, 1990). It has also been approved for the treatment of anaemia associated with cancer, HIV infection, and use in the surgical setting to decrease the need for allogeneic blood transfusions.…”

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confidence: 99%

Development and characterization of novel erythropoiesis stimulating protein (NESP)

2001

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Studies on human erythropoietin (EPO) demonstrated that there is a direct relationship between the sialic acid-containing carbohydrate content of the molecule and its serum half-life and in vivo biological activity, but an inverse relationship with its receptor-binding affinity. These observations led to the hypothesis that increasing the carbohydrate content, beyond that found naturally, would lead to a molecule with enhanced biological activity. Hyperglycosylated recombinant human EPO (rHuEPO) analogues were developed to test this hypothesis. Darbepoetin alfa (novel erythropoiesis stimulating protein, NESP, ARANESP TM , Amgen Inc, Thousand Oaks, CA), which was engineered to contain 5 N-linked carbohydrate chains (two more than rHuEPO), has been evaluated in preclinical animal studies. Due to its increased sialic acid-containing carbohydrate content, NESP is biochemically distinct from rHuEPO, having an increased molecular weight and greater negative charge. Compared with rHuEPO, it has an approximate 3-fold longer serum half-life, greater in vivo potency, and can be administered less frequently to obtain the same biological response. NESP is currently being evaluated in human clinical trials for treatment of anaemia and reduction in its incidence.© 2001 Cance Cance Cancer Research Campaign

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“…Using this preparation, the present study has clearly demonstrated that rHuEPO has no direct effects on MAP or renal hemodynamics in anesthetized rabbits without renal failure. Since molecular cloning and expression of a biological active form into mammalian cells (Jacobs et al 1985 ;Lin et al 1985), rHuEPO has been used clinically for treatment of anemia associated with chronic renal failure (Winearls et al 1986;Eschbach et al 1987;Mayer et al 1988). rHuEPO has been shown to be effective in reversing anemia in hemodialysis patients.…”

Section: Discussionmentioning

confidence: 99%

“…rHuEPO has been shown to be effective in reversing anemia in hemodialysis patients. Nevertheless, the major side effect is the development or worsening of hypertension in a cosiderable proportion of rHuEPO-treated patients (Winearls et al 1986 ;Bommer et al 1987 ;Eschbach et al 1987 ;Jacquot et al 1987 ;Raine 1988). The mechanism by which rHuEPO induces hypertension has been in the past explained by an increase of blood viscosity strongly related to the hematocrit (Mayer et al 1988 ;Raine 1988), or vasoconstriction elicited by improvement of hypoxia (Eschbach et al 1987 ;Kamata et al 1991).…”

Section: Discussionmentioning

confidence: 99%