Novel tissue remodelling roles for human recombinant erythropoietin

2005 ◽  
Vol 33 (5) ◽  
pp. 1129 ◽  
Author(s):  
S. Baig ◽  
P.J. Coussons ◽  
C. Fanutti ◽  
R. Grant
Keyword(s):  
Recombinant Erythropoietin ◽  
Tissue Remodelling ◽  
Human Recombinant Erythropoietin

Novel tissue remodelling roles for human recombinant erythropoietin

2005 ◽  
Vol 33 (5) ◽  
pp. 1129-1130 ◽  
Author(s):  
P.J. Coussons ◽  
S. Baig ◽  
C. Fanutti ◽  
R. Grant
Keyword(s):  
Multiple Roles ◽  
Chronic Congestive Heart Failure ◽  
Recombinant Erythropoietin ◽  
Tissue Remodelling ◽  
Human Recombinant Erythropoietin ◽  
Cellular Processes ◽  
Human Erythropoietin ◽  
Chronic Anaemia ◽  
Broad Array ◽  
Exciting Possibility

rHuEPO (recombinant human erythropoietin) is a haemopoietic growth factor and a primary regulator of erythropoiesis that is used for the treatment of chronic anaemia associated with RA (rheumatoid arthritis). Erythropoietin also appears to modulate a broad array of cellular processes, including progenitor stem-cell development, cellular integrity, angiogenesis and oxidative damage. These diverse activities suggest the exciting possibility of multiple roles for rHuEPO therapy in a variety of disorders other than RA, including cerebral ischaemia, myocardial infarction, chronic congestive heart failure and cancer. Thus it appears that rHuEPO may be a pleiotropic agent, capable of influencing tissue remodelling independently of its established erythropoietic role. Whereas these effects may be largely beneficial, dose-related side effects could have implications for the safe therapeutic use of rHuEPO and its illegal use as a performance-enhancing agent in endurance sports.

scholarly journals Clinical pharmacology and economics of recombinant human erythropoietin in end-stage renal disease: the case for subcutaneous administration.

1992 ◽  
Vol 2 (9) ◽  
pp. 1405-1416
Author(s):  
A Besarab ◽  
K K Flaharty ◽  
A J Erslev ◽  
J B McCrea ◽  
P H Vlasses ◽  
...  
Keyword(s):  
Clinical Pharmacology ◽  
Subcutaneous Administration ◽  
Entire Group ◽  
Pharmacokinetic Studies ◽  
Weekly Dose ◽  
Recombinant Erythropoietin ◽  
Dialysis Patients ◽  
Human Recombinant Erythropoietin ◽  
Human Erythropoietin ◽  
Stage Renal Disease

The clinical pharmacology of human recombinant erythropoietin (epoetin) was studied in order to compare the effectiveness of various routes and dosing schedules in dialysis patients. Thirty-six patients received epoetin beta three times a week i.v. for at least 12 wk. The mean dose needed to achieve target hemoglobin was 225 +/- 36 U/kg per week (median dose, 180 U/kg per week). Twenty-eight of 36 patients who were converted to a once-a-week i.v. schedule increased their requirements to 429 +/- 50 U/kg per week in order to maintain a target hematocrit of 33 to 40 vol%. Twelve of 28 patients could maintain their target hematocrit when dosed once a week s.c. at 84 +/- 10 U/kg. The other 16 patients required 137 +/- 15 U/kg per week divided into two doses. In the entire group of 28 patients, the weekly requirement for epoetin was reduced by 50% when the s.c. route was used two or three times a week. Pharmacokinetic studies performed during chronic therapy indicated rapid clearance of erythropoietin (t1/2 of 6.8 +/- 0.3 h). Single i.v. doses greater than 150 U/kg were required to increase basal erythropoietin by 30 mU/mL at 44 h postdosing. With s.c. dosing, such increments in erythropoietin levels frequently persisted beyond 60 h because of prolonged and slow absorption. Pharmacokinetic simulations in conjunction with clinical correlation of the erythropoietic response suggest that the duration that the erythropoietin levels are maintained, and not the absolute peaks, is the primary determinant of efficacy. This may result from nonlinearity in the dose response. Pharmacokinetic simulation also indicated that i.v. dosing could not maintain adequate interdialytic erythropoietin levels, whereas s.c. dosing could. Cost analysis indicated that the use of s.c. dosing two or three times a week at an average total weekly dose of 110 to 120 U/kg is effective treatment of anemia in most dialysis patients.

scholarly journals Flanker task-elicited Event Related Potential sources reflect human recombinant Erythropoietin differential effects on Parkinson’s patients

2019 ◽  
Author(s):  
Maria L Bringas Vega ◽  
Shengnan Liu ◽  
Min Zhang ◽  
Ivonne Pedroso Ibañez ◽  
Lilia M. Morales Chacon ◽  
...  
Keyword(s):  
Flanker Task ◽  
Reaction Times ◽  
Event Related Potential ◽  
Source Analysis ◽  
Random Allocation ◽  
Recombinant Erythropoietin ◽  
Human Recombinant Erythropoietin ◽  
Human Erythropoietin ◽  
Eeg Source Analysis ◽  
Eeg Recordings

AbstractWe used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson’ s Disease patients.The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low-resolution tomography (LORETA) inverse solution was employed to localize the neural generators.Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs.From our results rHuEPO, seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus evoked by incongruent stimuli differentiated PD and HCs.

scholarly journals Anemia in peritoneal dialysis patients

2006 ◽  
Vol 134 (3-4) ◽  
pp. 133-137 ◽  
Author(s):  
Mirjana Lausevic ◽  
Vidosava Nesic ◽  
Natasa Jovanovic ◽  
Biljana Stojimirovic
Keyword(s):  
Peritoneal Dialysis ◽  
Blood Count ◽  
Iron Supplementation ◽  
Transferrin Saturation ◽  
Recombinant Erythropoietin ◽  
Dialysis Patients ◽  
Human Recombinant Erythropoietin ◽  
Iron Stores ◽  
Number Of Patients ◽  
Significant Difference

A normocytic normochromic anemia is one of the first signs of renal failure. Since anemia increases morbidity and mortality, its elimination is one of the essential objectives of the treatment. Human recombinant erythropoietin (rHuEPO) has changed the therapeutical approach to anemia. The aim of the present study was to compare efficacy of anemia correction in peritoneal dialysis patients depending on treatment and dialysis modality. The study is the retrospective analysis of 64 patients who presented to our Clinic in 2003. Eighteen (28.13%) patients were treated with rHuEPO, 14 (28%) underwent continuous ambulatory peritoneal dialysis (CAPD), 2 (100%) - automated peritoneal dialysis (APD) and 2 (33.3%) - intermittent peritoneal dialysis (IPD). Mean hemoglobin level was 98.6?17.82 g/l in patients treated with rHuEPO versus 98.81?15.14 g/I in patients without rHuEPO treatment. Erythropoietin requirements were 3392.85?1211.77 IU/week. AII patients received iron supplementation during rHuEPO therapy. Mean serum ferritin levels were 463.41 ?360 ?g/l. Transferrin saturation (TSAT) was 0.35?0.16%. No difference of serum iron and TSAT levels was found between CAPD and IPD patients. The degree of anemia significantly differed between CAPD and IPD patients. A total of 17.11% of PD patients were given blood transfusions, most frequently during the first three months after the onset of dialysis. Our conclusion is that the number of patients receiving rHuEPO should be increased, as 50% of our patients should be substituted, while only 28% are being treated. As 50% of patients receiving rHuEPO failed to reach target Hgb levels, higher EPO doses should be considered. Iron stores should be continuously monitored, particularly in patients receiving rHuEPO, since iron deficiency is an important problem for patients undergoing peritoneal dialysis, especially during erythropoietin therapy. Oral iron supplementation is satisfactory in the majority of patients, and iron-gluconate is absorbed better than iron-sulphate. If required, intra-venous iron bolus is safe and efficient. Continuous peritoneal dialysis treatment improves blood count more effectively compared to intermittent procedures, as hemoglobin levels are significantly higher in patients with comparable iron stores. Peritoneal dialysis is particularly efficient in improving the blood count in diabetics, since no significant difference of anemia between patients affected by diabetes mellitus and the others could be found in our study.

scholarly journals Higher dose of erythropoietin for anemia correction in Balkan endemic nephropathy patients

2012 ◽  
Vol 140 (7-8) ◽  
pp. 456-461
Author(s):  
Ljiljana Lukic ◽  
Djordje Mitrovic ◽  
Sanda Kovacevic ◽  
Momir Stanisic ◽  
Snezana Pelemis ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Ferritin Level ◽  
Hemoglobin Level ◽  
Obstructive Nephropathy ◽  
Balkan Endemic Nephropathy ◽  
Recombinant Erythropoietin ◽  
Severe Anemia ◽  
Human Recombinant Erythropoietin ◽  
Endemic Nephropathy ◽  
Regular Hemodialysis

Introduction. Balkan endemic nephropathy (BEN) patients maintained with hemodialysis have more severe anemia than patients with other kidney diseases. Objective. The aim of the study was to compare the improvement of anemia in BEN patients and those with other kidney diseases during treatment with human recombinant erythropoietin (rHuEpo). Methods. The study involved 240 patients on regular hemodialysis for more than one year. Out of them 146 had BEN and 94 other kidney diseases (21 glomerulonephritis, 20 hypertension, 18 diabetes, 10 policystic kidney disease, 5 obstructive nephropathy, 18 other diseases). Treatment with rHuEpo was carried out according to European guidelines for the management of anemia. Results. Patients with BEN were older and were less frequently treated with ACEi than patients with other kidney diseases. At the onset of the study mean hemoglobin level (109.6?22.3 vs. 112.7?11.3 g/l) was significantly lower, but serum ferritin level and rHuEpo dose (65.4?22.3 vs. 57.5?22.5 U/kg/week) were significantly higher in BEN patients than in others. In prospective four months study these differences in hemoglobin levels and rHuEpo doses maintained. The rate of anemia improvement was examined in 15 BEN patients and 10 patients with other kidney diseases at the beginning of rHuEpo treatment. No difference in the rate of anemia improvement was found between the two groups but higher rHuEpo doses were used in BEN patients. Conclusion. Patients with BEN on regular hemodialysis had more severe anemia and required higher rHuEpo doses for maintaining target hemoglobin level.

Role of Haematocrit in Mediating the Actions of Chronic Erythropoietin Treatment on Blood Pressure and Renal Haemodynamics in the Rat

1993 ◽  
Vol 85 (6) ◽  
pp. 717-724 ◽  
Author(s):  
Chunlong Huang ◽  
Gerard Davis ◽  
Edward J. Johns
Keyword(s):  
Blood Pressure ◽  
Direct Action ◽  
Chronic Administration ◽  
Treated Group ◽  
Recombinant Erythropoietin ◽  
Doppler Flowmetry ◽  
Human Recombinant Erythropoietin ◽  
Vascular Responsiveness ◽  
Erythropoietin Treatment ◽  
Renal Vascular

1. This investigation aimed to study the effect of chronic administration of human recombinant erythropoietin on haematocrit, blood pressure, renal cortical and papillary resistances and vascular responsiveness to vasoconstrictor agents. 2. Rats were treated with placebo or 25, 50 or 100 units/kg erythropoietin subcutaneously, every other day for 3 weeks. Animals were then anaesthetized with sodium pentobarbitone and were prepared for laser-Doppler flowmetry measurement in the renal cortex and papilla. 3. Haematocrit in the placebo-treated group was 48.0 + 0.5% and was raised to 52.5 + 0.7, 55.9 + 0.8 and 62.4 + 1.1% (all P <0.05) by the chronic administration of 25, 50 and 100 units/kg doses of the hormone, respectively. Blood pressure was 107 + 1 mmHg in the placebo-treated group and was elevated to 116 + 2 and 130 + 1 mmHg (both P <0.05), respectively, by the two highest doses of erythropoietin. Cortical and papillary perfusions were reduced at the highest dose of erythropoietin, but calculated resistances were increased by 15 and 40% (P <0.05) at 50 and 100 units/kg doses of the hormone, respectively. 4. Infusion of the vasopressor hormones vasopressin and phenylephrine caused increases in blood pressure and decreases in renal cortical and papillary perfusion, the magnitudes of which were only marginally changed by the highest dose of the erythropoietin. Angiotensin II increased blood pressure and decreased cortical perfusion, and the magnitudes of these responses were unchanged by the chronic treatment with erythropoietin. 5. Acute graded increases in haematocrit resulted in significantly (P <0.05) raised blood pressure above a value of 58%. However, renal cortical and papillary perfusions decreased and resistances were increased significantly (P <0.05) when the haematocrit was raised above 56%. 6. The acute transfusion study demonstrated that elevations in blood pressure and renal vascular resistances occurred at haematocrit values somewhat higher than when it was raised by chronic erythropoietin treatment. Thus this would be consistent with the suggestion that erythropoietin has some direct action on the vasculature beyond that resulting from the raised haematocrit. These data show that a low dose regimen of erythropoietin can modestly increase haematocrit without other cardiovascular changes becoming apparent. The findings add weight to the recent clinical practice of using very low doses of the hormone in the treatment of chronic renal failure.

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