ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02565.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The production of recombinant human erythropoietin (r‐HuEPO) began with a search for the gene coding for human erythropoietin (EPO). Two radiolabeled pools of oligonucleotide probes were designed, based on amino acid sequence information obtained from human urinary EPO. Each probe, consisting of complex mixtures of 128 short synthetic sequences of DNA, was used to search a human genomic library for clones containing the human EPO gene sequence. To verify that the isolated clones contained the complete functional gene encoding human EPO, these sequences were expressed in Chinese hamster ovary cells, and the secreted r‐HuEPO was purified, characterized, and compared with the human urinary hormone using a variety of different techniques. Results of these studies indicate that r‐HuEPO is virtually indistinguishable from human urinary EPO in its biochemical and immunological properties. It is a 165‐amino acid protein whose primary sequence is identical to that of urine‐derived EPO. The subsequent development of large‐scale cell culture and production techniques has made available sufficient amounts of r‐HuEPO for clinical use in the treatment of the debilitating anemia that almost invariably accompanies chronic

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02566.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Recombinant human erythropoietin reverses the severe anemia associated with end‐stage renal disease. Mean half‐life values after a single intravenous bolus dose range from 4–13 hours. Renal clearance is not a significant route of elimination. Dosing schedules in chronic renal failure involve a single intravenous bolus dose administered three times weekly after hemodialysis. Subcutaneous dosing has been approved and may be used in patients without intravenous access. Reticulocyte counts and hematocrit levels exhibit dose‐dependent increases; improved hematocrit levels can be sustained with maintenanc

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02567.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The efficacy of epoetin alfa (recombinant human erythropoietin) has been tested for treating the anemia associated with end‐stage renal disease. This anemia is caused by severely decreased levels of erythropoietin, 90% of which is ordinarily produced by healthy kidneys. Treatment with epoetin alfa successfully corrected the anemia of 97% of 333 patients, as evidenced by hematocrit levels that increased by at least 6 percentage points or reached a study target level of 35%, 2 points above current guidelines. The 127 patients who previously required red cell transfusions to maintain an adequate hematocrit became completely transfusion independent after receiving epoetin alfa. Furthermore, treatment with this growth factor alleviated many of the symptoms of uremia, such as loss of energy and appetite. The major side effect observed with epoetin alfa treatment was increased diastolic blood pressure; however, this was well controlled by additional antihypertension medication. There have been no reports of antibody formation in response to this drug. Thus, epoetin alfa is a safe and effective means of treating the anemia caused by chronic renal insufficienc

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02568.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Epoetin alfa (recombinant human erythropoietin) effectively diminishes the anemia associated with end‐stage renal disease (ESRD). Although many clinical manifestations of ESRD have been attributed to uremic toxins, the ability of epoetin alfa therapy to improve several of these conditions, such as diminished energy levels, appetite, cold tolerance, sexual function, and cognitive abilities, suggests that anemia may be an important factor in uremia‐associated symptoms. Correction of this anemia results in improvements in the patient's quality of life. These improvements can be measured by objective criteria such as exercise tolerance tests, or by subjective standards such as patient response to questionnaires. In studies to date, both subjective and objective data show that epoetin alfa therapy significantly improves the quality of life of patients with E

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02569.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02571.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY