UMLS:C0020538 - FACTA Search

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The anemia associated with end-stage renal disease (ESRD) is primarily due to a deficiency in renal-derived erythropoietin. Through advances in genetic engineering, the gene for erythropoietin has been isolated and cloned, and recombinant human erythropoietin (r-HuEPO; EPOGEN, AMGEN Inc, Thousand Oaks, CA) is now available for clinical use. Study results indicate that r-HuEPO is highly effective in ameliorating symptomatic anemia in patients with chronic renal failure. Sustained dose-dependent increases in hematocrit values are achieved in at least 97% of patients, with improvement in quality of life, exercise tolerance, decrease in total body iron stores, and virtual elimination (40-fold reduction) of transfusion requirements. Hypertension is the most common side effect, but is easily controlled. To date, anti-erythropoietin antibodies have not been detected in patients treated with this product. Doses between 100 and 150 U/kg body weight are sufficient to increase hematocrit levels to normal in 2 months or less, with iron replacement therapy needed in most patients. The correction of anemia in ESRD patients promotes an increase in appetite, causing ingestion of more protein, potassium, and sodium. The resulting need for increased dialysis may burden existing dialysis facilities. Experience with 36 patients receiving r-Hu-EPO demonstrates that high-flux short-time hemodialysis is as effective as conventional hemodialysis. There were no significant differences between the groups in laboratory parameters including blood urea nitrogen, creatinine, potassium, phosphate, mean arterial pressure, and weight loss, although hematocrit values were slightly higher in the high-flux dialysis patients. Adverse effects resulting from r-HuEPO treatment were minor and were not more common in the group receiving high-flux short-time hemodialysis.
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PMID:Clinical efficacy of recombinant human erythropoietin in hemodialysis patients. 264 16

The development of hypoproliferative anemia with generally normocytic red blood cells in most patients with chronic renal failure impairs the success of maintenance dialysis therapy, particularly hemodialysis. Anemia can be a complication of the hemodialysis procedure itself, with its associated blood losses and mild effect on oxygen transport functioning. However, the primary cause of anemia in the chronic dialysis patient is decreased erythropoiesis. The most important mechanism leading to decreased erythropoiesis involves the production of subnormal levels of erythropoietin (EPO). Insufficient nephric output of EPO or, possibly, suppression of the effect of EPO by uremic inhibitors may cause this decreased erythropoiesis. Other factors, such as iron deficiency, hyperparathyroidism, systemic infections, and aluminum toxicity may contribute to anemia in some patients. Increased hemolysis, a comparatively mild factor in the anemia of chronic dialysis patients, may be related to retention of protein metabolism products, hypersplenism, hypophosphatemia, drugs, or other conditions in affected patients. There are several traditional treatment options for anemia: transfusions; iron, vitamin B12, or folic acid supplementation when indicated; a change to peritoneal dialysis; parathyroidectomy; and administration of androgens. None of these treatments have proved satisfactory, and some, such as transfusions and androgen therapy, pose risks and have serious side effects. A comparatively new approach, administration of genetically engineered erythropoietin (r-HuEPO; EPOGEN, AMGEN inc, Thousand Oaks, CA), has been found effective in treating anemia in clinical trials. Patients have shown improved cardiac performance as well as enhanced quality of life, and hypertension appears to be the most serious side effect of r-HuEPO therapy.
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PMID:Overview of anemia associated with chronic renal disease: primary and secondary mechanisms. 264 18

Preeclampsia, a major cause of fetal and maternal morbidity and mortality, may be difficult to distinguish clinically from other hypertensive disorders of pregnancy. Signs helpful in its diagnosis include presentation during late gestation in a nullipara with edema and proteinuria, and one or more of the following: hemoconcentration, hypoalbuminemia, liver function and/or coagulation abnormalities, and increased urate levels. Measures that may prove useful in differentiating preeclampsia from less dangerous forms of hypertension are decreased antithrombin III levels, increments in serum iron and carboxyhemoglobin, and decreases in urinary calcium. Major pathophysiological features of preeclampsia are decreased cardiac output, pulmonary capillary wedge pressure, and plasma volume; and marked increases in peripheral vascular resistance, as well as exaggerated pressor responses to endogenous angiotensin II and catecholamines. Renal hemodynamics decrease, in part as a result of a characteristic morphological lesion in glomeruli ("endotheliosis"), and there may be increased vascular permeability leading to albumin loss from the intravascular space. When gestation is advanced, termination is the treatment of choice; when temporization is required, several antihypertensive medications whose safety and efficacy have been tested in pregnant women are available. Magnesium sulfate remains the drug of choice for impending convulsions (the eclamptic phase of the disease). Finally, the etiology of preeclampsia remains unknown, but a popular theory suggests that alterations in prostaglandin metabolism may be responsible for the hypertension and coagulopathy in this disorder. In this respect, prophylactic treatment with low doses of aspirin, which decrease platelet thromboxane production but spare endothelial prostacyclin release, may decrease the incidence of preeclampsia in "high-risk" populations.
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PMID:Preeclampsia: pathophysiology, diagnosis, and management. 265 50

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

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

Preeclampsia is a complication of pregnancy characterized by hypertension, edema and proteinuria, beginning after 20 weeks of gestation. Six percent of the pregnant women in North America develop this disease, which is associated with increased morbidity and mortality for the mother and her baby. The physiopathology remains uncertain despite many research efforts. Actual hypotheses seek to explain the vasospasm that characterizes the disease. Among the many factors influencing vascular reactivity and possibly implicated are: the renin-angiotensin system, prostaglandins, progesterone and its metabolites, calcium, magnesium, digoxin-like immunoreactive substance(s), auricular natriuretic factor, substances secreted by platelets and leukotrienes. Prevention of the disease is limited by the absence of a biological or clinical marker with good sensitivity and appropriate specificity. Many biochemical or hematological parameters have been reported: uric acid, calcium, magnesium, proteinuria, blood iron, hematocrit, platelet count, antithrombin III, estrogen and progesterone. The combination of several tests could be superior to the use of each test individually, providing a better sensitivity and improving the positive predictive value. With early detection, new therapies for the prevention of the disease could be experimented on the higher risk women before the apparition of clinical symptoms or signs. Furthermore, those tests could be used in the study of the pathophysiology and in the choice of the best therapy.
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PMID:[Preeclampsia: physiopathology and prospects for early detection]. 269 75

Epoetin (recombinant human erythropoietin) is a sialoglycoprotein hormone that appears to be immunologically and biologically equivalent to the endogenous compound, enhancing erythropoiesis dose-proportionally. The therapeutic efficacy of epoetin in the treatment of anaemia associated with chronic renal failure has been established, with almost all patients responding with increases in haematocrit and haemoglobin levels, and improvements in quality of life. Some patients demonstrate relative epoetin resistance and require a higher dosage to achieve target haemoglobin and haematocrit levels. Maintenance of an adequate iron supply is essential and iron supplementation is recommended if serum ferritin is below 100 to 150 micrograms/L or transferrin saturation is less than 20%. The incidence of serious adverse effects may be reduced by maintaining a moderate rate of increase in the haematocrit with close monitoring of blood pressure and dialysis efficacy. Individual titration of epoetin dosage is recommended, with increases made in small increments to achieve haematocrit and haemoglobin levels of 30 to 33% and 10 to 12 g/dl, respectively, although the optimal haematocrit for each patient should be individually determined. Some patients will also require a modest increase in heparin dosage because of a possible increase in clotting tendency. Hypertension is the most common adverse effect in patients with chronic renal failure, occurring partially as a result of increasing blood viscosity and peripheral vascular resistance with the correction of anaemia. Maintenance epoetin therapy has been given for more than 2 years without a decrease in responsiveness and does not appear to adversely affect the outcome of renal transplantation. Thus, epoetin represents a significant therapeutic advance in the treatment of anaemia associated with chronic renal failure and should be considered a first option for these patients. Its potential value in the treatment of anaemia associated with other disorders and in facilitating autologous blood donation remains to be fully determined.
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PMID:Epoetin (recombinant human erythropoietin). A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in anaemia and the stimulation of erythropoiesis. 269 45

18 anemic patients undergoing maintenance hemodialysis were treated with recombinant human erythropoietin (EPO) 1-3 times per week for 10.7 +/- 3 months. 4 patients underwent renal transplantation whereas 14 patients could be followed up during 12 months of EPO treatment. Hemoglobin concentration rose (from 7.0 +/- 0.7 to 11.0 +/- 1.1 g/dl, p less than 0.001) with an EPO maintenance dose of 298 units/kg/week. Blood transfusions were totally eliminated. 12 patients without iron overload required iron supplements. In the course of an infectious episode and notwithstanding an increase in EPO dosage, 2 patients exhibited a fall in hemoglobin which rose again after successful treatment of the infection. The few complications observed in connection with the rise in hemoglobin were: 1. deterioration of arterial hypertension in 7/18 with hypertensive encephalopathy in 3 patients, 2. thrombotic occlusion of the vascular hemodialysis access (a-v fistula) in 3/18, 3. periarticular inflammation with calcified deposits due to an elevated calcium-phosphorus product of 6.8 mmol/l in 4/18, 4. occurrence of hyperkalemia (6.9 +/- 0.3 mmol/l) in 7/18. These complications were more frequent during the first 3 months. They were corrected with close monitoring, drug therapy for hypertension, and intensification of dialysis and of treatment with phosphate binding substances, with the result that no differences were found in 14 patients before and after 12 months of treatment with EPO (blood pressure 133 +/- 25/77 +/- 9 vs 139 +/- 26/79 +/- 13 mm Hg [ns], potassium 5.4 +/- 0.4 vs 5.6 +/- 1.0 mmol/l [ns] and calcium-phosphorus product 4.3 +/- 1.0 vs 4.6 +/- 1.3 [ns]).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of anemia in hemodialysis patients using recombinant human erythropoietin: advantages and disadvantages]. 271 Nov 61

The quality of life was assessed in 37 maintenance hemodialysis patients during treatment with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) for correction of anemia. All patients experienced an increase in hematocrit level. The mean hematocrit level in the study population was 19.8% before therapy and 31.5% after therapy. Eighty-four percent of patients reported an increase in their sense of well-being. Better appetite was subjectively noted by 81% of patients. Improvements in sexual function (62%), socializing (70%), sleep (68%), and skin color (51%) were also noted. An increase in exercise capacity was reported by 78% of patients; objective measurements showed that the mean value of VO2max in a subgroup of 11 patients increased by 50% after treatment. The Karnofsky score calculated in 29 patients showed improvement in all patients except those aged greater than 70 years. The group mean Karnofsky score increased from 76 before to 86.6 after therapy, indicating that with r-HuEPO treatment subjects were able to exert themselves to perform ordinary activities. Before therapy 14 of the patients were unemployed; after therapy only two did not work. Those side effects that occurred, predominantly iron deficiencies, hypertension, and hyperkalemia, were controlled by appropriate clinical management. Treatment with r-HuEPO does improve the quality of life and ability to work of uremic patients and does not adversely affect their transplant potential.
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PMID:Improvements in quality of life following treatment with r-HuEPO in anemic hemodialysis patients. 275 25

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