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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythrocytosis after renal transplantation confers risks of thromboembolic complications and therefore necessitates repeated phlebotomies and/or anticoagulation therapy. Erythropoietin production from the retained native kidneys is one aetiological possibility for this condition. During 1982-1987, 22 patients with renal transplants underwent bilateral nephrectomy because of erythrocytosis with a median duration of 13 months. The median follow-up time was 36 months. After nephrectomy, blood counts returned to normal in all patients; these remained normal in all but two patients, who relapsed with erythrocytosis after 6 and 18 months respectively. Concomitant hypertension was cured or improved in most cases. One patient had a myocardial infarction postoperatively. No other per- or postoperative complications occurred. The mean duration of hospital stay was 7.5 days. We consider bilateral nephrectomy of the native kidneys a safe and effective alternative in the management of post-transplant erythrocytosis.
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PMID:Erythrocytosis after renal transplantation; treatment by removal of the native kidneys. 212 35

Erythropoietin is a glycoprotein hormone of primarily renal origin that promotes the proliferation and differentiation of erythrocyte precursors. Technological advances have resulted in the production of recombinant hormone suitable for therapeutic use and have permitted significant progress in the characterization of the physiologic and pathologic processes involved in endogenous erythropoietin production. In situ hybridization studies have shown that erythropoietin production in the hypoxic kidney occurs primarily in peritubular cells, most likely endothelial cells. In renal carcinoma associated with polycythemia, however, erythropoietin mRNA has been detected in the tumor cells, which are tubular in origin. New information regarding the biochemistry of the erythropoietin receptor has been gleaned subsequent to the cloning of the gene encoding the receptor; however, much remains to be learned about the interaction of the hormone with its target cells. With regard to clinical experience, recombinant erythropoietin has been shown to correct the anemia associated with chronic renal failure in patients requiring dialysis, having a significant beneficial effect on the overall physical and psychological state of the patient; the major adverse effect of such treatment is hypertension. The role of recombinant erythropoietin in predialysis patients, patients with anemias of other origin, and other clinical settings is currently being evaluated.
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PMID:Erythropoietin: physiology and clinical experience. 219 61

Extensive testing has proven that recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) corrects the anemia of end-stage renal disease and eliminates the need for transfusions in virtually all patients. Patients whose hematocrit levels are less than 0.30 or who are transfusion dependent are candidates for therapy. A dosage of 50 to 150 U/kg body weight intravenously three times a week produces an increase in hematocrit by approximately 0.01 to 0.02 per week. Once the hematocrit reaches 0.30 the dose is adjusted so that a target hematocrit of 0.32 to 0.38 is maintained. Eighty percent of patients need maintenance doses of r-HuEPO of less than or equal to 150 U/kg; the other 20% of patients require larger doses. Reasons for poor responses include iron deficiency, inflammation due to surgery or infection, and osteitis fibrosa. Most patients require iron supplementation to prevent functional iron deficiency. BP increased in one third of patients, and in 3% seizures occurred during the initial phase of therapy, often associated with a sudden increase in BP. This hypertension can be controlled with medication. Increased dialyzer clotting may occur, which is prevented when heparin doses are adjusted, and dialyzer solute clearances may decrease slightly. Treatment with r-HuEPO does not elicit an antibody response. The mechanism of action of r-HuEPO is identical to that of natural erythropoietin, and therefore is an appropriate therapy for the long-term management of anemia in chronic renal failure.
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PMID:Guidelines for recombinant human erythropoietin therapy. 266 49

Effective monitoring of chronic hemodialysis patients treated with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) includes an initial evaluation of the patient, the patient's anemia, and the patient's iron stores. Assessment of iron stores includes obtaining hematocrit and hemoglobin levels, reticulocyte count, red cell indices, serum ferritin level, transferrin percent saturation, and the patient's transfusion history. If iron stores are inadequate to support the increased erythropoiesis induced by the therapy, appropriate iron replacement therapy should be provided. Monitoring also involves assessment of BP (and its control), because development or exacerbation of hypertension is the most significant side effect associated with this treatment. Because the dose-response relationship for r-HuEPO therapy has been clearly documented, a target hematocrit and target rate of increase in hematocrit can be established. As anemia improves, continued monitoring of hematocrit, hemoglobin, red cell indices, serum ferritin level, and transferrin percent saturation will ensure that depleted iron stores are noted and treated as necessary. Heparin requirements during dialysis, blood chemistries, and blood access problems should also be monitored. No data currently exist suggesting that dialyzer reuse is compromised by r-HuEPO therapy. Quality-of-life surveys show improvement with r-HuEPO treatment and effective reduction of anemia. There is also some indication that morbidity is lessened and survival improved when anemia is treated with r-HuEPO therapy.
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PMID:Monitoring considerations in recombinant human erythropoietin therapy. 266 80

Onset or exacerbation of hypertension has been observed as a possible complication of recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) therapy for the anemia of end-stage renal disease. This effect is attributed to an overly rapid rise in the hematocrit level and the accompanying consequences, which include increased hemoglobin, blood viscosity, and red cell mass, as well as normalization of the cardiac index of anemia. The sluggish response to these changes by compensatory mechanisms, resulting in increased peripheral vascular resistance, may be the means by which BP becomes elevated during therapy. Although more than one third of patients receiving r-HuEPO therapy have developed sustained increases in diastolic pressure of 10 mmHg or more, this potential problem is controllable. Prevention or correction of hypertension is accomplished by initiating therapy with a low-dose regimen that is slowly increased, thereby preventing a rapid rise in the hematocrit level. Drug intervention, together with dialysis prescription modification and restriction of dietary salt and fluid to regulate weight, can effectively control BP. Discontinuation of therapy for severe and uncontrollable hypertension rarely becomes necessary.
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PMID:Management of blood pressure changes during recombinant human erythropoietin therapy. 266 81

The treatment of severe anemia related to end-stage renal disease with recombinant human erythropoietin (r-HuEPO; EPOGEN, [epoetin alfa] AMGEN Inc, Thousand Oaks, CA) has been investigated in more than 1,500 hemodialysis patients worldwide. The goal of r-HuEPO therapy is to maintain the hematocrit level at 35%, with a recommended starting dose of 150 mg/kg of body weight, administered intravenously after each dialysis three times a week for 6 to 12 weeks. Hematocrit levels should be measured at least once a week and the dose adjusted in increments or decrements of 10 mg/kg to 25 mg/kg to keep the hematocrit level between 33% and 40%. Patients receiving r-HuEPO must be normotensive. A history of seizures has been cause for exclusion from clinical trials. Patients' iron status should also be adequate at the onset of therapy, which is defined as a serum ferritin level of 100 ng/mL or more, and a transferrin saturation of more than 20%. Iron status and BP must be carefully monitored, and abnormalities corrected with iron supplementation, ultrafiltration, or antihypertensive medication. The lack of controlled studies makes determination of the actual incidence of side effects difficult, but it appears to be minimal. Possible side effects of r-HuEPO therapy include hypertension, seizures, myalgia, malaise, headache, gastrointestinal distress, and injected conjunctiva. The major benefits of r-HuEPO therapy are reduced need for transfusion and marked improvement in quality-of-life parameters.
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PMID:Who should receive recombinant human erythropoietin? 266 84

Erythropoietin is produced mainly by the kidneys and stimulates erythropoiesis in the bone marrow. Chronic renal failure is characterized by anemia, which is principally caused by erythropoietin deficiency. Recombinant human erythropoietin (r-hEPO) corrects the anemia of chronic renal disease and improves patient well-being, exercise tolerance, and cognitive function. The clinical pharmacology, efficacy, safety, and tolerance of r-hEPO are presented. Four major studies attest to r-hEPO's efficacy in the treatment of anemia of chronic renal disease and document potential toxicities of hypertension, iron deficiency, thrombosis, and bone pain. Careful attention to the extent of correction of the hematocrit, increased heparinization during hemodialysis therapy, and compliance with dietary restrictions may minimize the incidence and severity of adverse reactions. Resistance to r-hEPO may be due to iron deficiency, aluminum toxicity, or inflammation, including infection. Potential future uses of r-hEPO include the treatment of various other anemias, such as those seen in sickle cell anemia, rheumatoid arthritis, and autologous blood donation. Controlled clinical studies in these areas have not been reported.
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PMID:Recombinant human erythropoietin. 266 69

The chemistry, pharmacology, pharmacokinetics, clinical uses and efficacy, adverse effects, drug interactions, dosage and administration, and formulary considerations of epoetin are described. Erythropoietin, a glycoprotein hormone primarily synthesized in the kidney, is the chief regulator of red blood cell production. Erythropoietin concentrations increase in response to a hypoxic state, resulting in increased red blood cell formation, accelerated hemoglobin production, and premature movement of reticulocytes into the circulation. The human gene responsible for the production of erythropoietin recently was cloned, and the recombinant product--epoetin--has been made available through mass production. The apparent volume of distribution of i.v. epoetin approximates the assumed plasma volume both in healthy volunteers and in patients with chronic renal failure. Little is known about the metabolism and route of elimination of epoetin and erythropoietin. Epoetin recently was approved by the FDA for treatment of anemia associated with chronic renal failure. Clinical trials in patients receiving hemodialysis or peritoneal dialysis and in predialysis patients with renal dysfunction demonstrate epoetin's efficacy. Other potential indications include augmentation of blood production in patients enrolled in autologous blood donation programs and treatment of anemias associated with rheumatoid arthritis, sickle cell disease, acquired immunodeficiency syndrome, cancer, and premature birth. The most frequent adverse effect associated with epoetin therapy is the worsening or development of hypertension. Other adverse effects include thrombocytosis, hyperkalemia, rise in serum urea concentration, iron deficiency, and flu-like symptoms. No drug interactions with epoetin have been reported in humans. The recommended starting epoetin dosage in patients with chronic renal failure is 50-100 IU/kg three times weekly. Epoetin is available only as an injection for i.v. or s.c. administration. Epoetin provides a new therapeutic approach to the treatment of anemia associated with chronic renal failure in hemodialysis, peritoneal dialysis, and predialysis patients. Benefits of epoetin therapy include reduced need for blood transfusions, the amelioration of anemic symptoms, and an improved quality of life.
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PMID:Epoetin: human recombinant erythropoietin. 268 Feb 41

Erythropoietin mRNA is detected primarily in kidney peritubular cells in response to hypoxia, and this tissue is the major adult source of the hormone. Erythropoietin can be assayed by in vivo or in vitro biological methods, or by radioimmunoassay, but only the in vivo assay can distinguish the most biologically active forms. The mature hormone consists of 166 amino acids and approximately 50% of the mature molecule (Mr 39,000) consists of carbohydrate. The gene is highly conserved among species studied, and is located on human chromosome 7, region q11-q22. Recombinant erythropoietin has been administered to haemodialysis patients and shown to increase haemoglobin levels, reticulocyte numbers and haematocrit. In transfusion-dependent patients, the need for regular transfusions was abrogated. Problems with hypertension have been noted in previously hypertensive patients, but the results of clinical trials with erythropoietin suggest that it will provide a valuable alternative therapy, for correcting some disorders of erythropoiesis.
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PMID:Erythropoietin. 268 15

The characteristics and uses of epoetin alfa (recombinant human erythropoietin) are described, and the issues associated with its use are discussed. The use of epoetin alfa was recently approved by FDA for the treatment of anemia associated with end-stage renal disease. Epoetin alfa acts on burst-forming and colony-stimulating units in the blood to raise hemoglobin and hematocrit levels, thus correcting the patient's anemia. It has a relatively short half-life and may be given either i.v. or s.c. Doses vary and must be adjusted according to the individual patient response. Clinical trials have involved doses ranging from 15 to 500 units/kg three times per week. Treatment causes a dose-related rise in the hematocrit, with subsequent improvement in the quality of life of dialysis patients. Adverse effects include hypertension, iron deficiency, and thrombocytosis. Additional research indicates that epoetin alfa may be effective in the correction of other uncomplicated anemias, such as those related to antineoplastic therapy. Issues facing hospital pharmacists and other health-care professionals include cost (the estimated cost of therapy is $4000 to $8000 per patient per year), appropriate use and potential misuse, use and reimbursement for indications not included in FDA-approved labeling, and restriction to particular prescribers. Because epoetin alfa does not produce therapeutic effects for at least 7 to 14 days, it is an ideal agent for formulary restriction. Epoetin alfa, like other products of biotechnology, will have substantial impact, both therapeutic and economic, on the practice of pharmacy. Hospital pharmacists need to be aware of these new therapies so that they may act quickly and decisively when issues associated with their use arise.
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PMID:Recombinant human erythropoietin. 269 Jun 6


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