Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The induction or the aggravation of a hypertension is a side effect of recombinant human erythropoietin therapy in 30% of dialysed patients. Clinical manifestations can be severe. Pathogenesis of erythropoietin-induced hypertension is ill known. Peripheral vascular changes were found in most studies. Recently, it was demonstrated that erythropoietin increased endothelin-1 release by endothelial cells. Ambulatory blood pressure recording seems to be the best method for evaluating the modification of blood pressure profile during the interdialytic period. Erythropoietin-induced hypertension is easily controlled by drugs, but also by low dose of erythropoietin. Subcutaneous administration of erythropoietin is an approach to avoid the induction of hypertension. Furthermore economical advantages of subcutaneous administration are proven.
 ...
PMID:[Erythropoietin and arterial hypertension in patients with chronic renal insufficiency]. 765 30

Epoetin alfa is a recombinant form of the principal hormone responsible for erythrogenesis, erythropoietin. Already an established treatment for anaemia associated with renal failure, epoetin alfa may also be used to correct anaemia in other patient groups. The drug increases the capacity for autologous blood donation in patients scheduled to undergo surgery and attenuates the decrease in haematocrit often seen in untreated autologous donors. However, transfusion requirements did not significantly decrease in many trials. Epoetin alfa also accelerates red blood cell recovery after allogeneic--but not autologous--bone marrow transplant. Limited data in patients with adult rheumatoid arthritis suggest that while epoetin alfa increases haematocrit/haemoglobin levels, overall clinical rheumatological status may not improve. However, the drug did improve quality of life in a small cohort of children with juvenile rheumatoid arthritis in addition to correcting anaemia. Response rates to treatment with epoetin alfa in patients with anaemia associated with cancer range between 32 and 85%. Anaemia associated with cancer chemotherapy also responds well to treatment with the drug as does anaemia associated with zidovudine therapy in patients with acquired immune deficiency syndrome (AIDS). Studies evaluating the use of epoetin alfa as treatment for anaemia of prematurity have used different methodologies and dosages, making overall analysis difficult. Nevertheless, it appears that high dosages are necessary for response. Results from 1 study suggest that treatment with epoetin alfa appears to be more costly than transfusional support in this application; the relevance of this finding is questionable, however, given that the aim of treatment with epoetin alfa is elimination of transfusion requirements. The incidence of many adverse events associated with epoetin alfa treatment in patients with renal failure (hypertension, seizures and thromboembolic events) has been minimal in patients without renal failure. Adverse events occurred at a similar rate in placebo and epoetin alfa recipients in placebo-controlled trials evaluating the use of the drug as treatment for anaemia in patients with cancer receiving chemotherapy or patients with AIDS receiving zidovudine. In summary, epoetin alfa is an effective alternative to blood transfusion, reducing anaemia and producing consequent improvements in quality of life in many nonrenal applications. It was more effective than placebo in a number of double-blind trials and may be particularly useful as treatment for anaemia associated with other drugs such as cisplatin and zidovudine.
 ...
PMID:Epoetin alfa. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in nonrenal applications. 772 31

The aim of this study was to investigate the mechanism of erythropoietin-induced hypertension in respect to its action on blood serotonergic system. The experiment was carried out on healthy rats and animals with experimental chronic renal failure. Erythropoietin (rHuEPO) injected into the healthy and uremic rats caused an increase in systolic blood pressure. This effect was completely abolished by ketanserin, an antagonist of 5-HT2 receptors. Concomitantly a rise in blood and platelet serotonin concentration was observed. It is concluded that serotonin may play a role in the development of hypertension caused by rHuEPO. Moreover, ketanserin may serve as a drug for pharmacological protection of rHuEPO-induced rise of blood pressure in uremia.
 ...
PMID:Serotonin is involved in the pathogenesis of hypertension developing during erythropoietin treatment in uremic rats. 774 May 14

Erythropoietin (Epo) is a glycoprotein hormone responsible for the control of the proliferation and differentiation of cells of erythroid lineage. Recombinant erythropoietin (rHuEpo) is widely used as a pharmacological agent for the treatment of the anaemia of renal failure. Efficacy of rHuEpo and its superiority over blood transfusions have been proven in large multicentre trials. The most important side-effect of the therapy is the increase of BP which is observed in approximately 30-35% of dialysis patients receiving rHuEpo. It appears that the haemodynamic resetting that occurs with partial correction of anaemia may be inappropriate resulting in an altered vascular resistance in relation to the cardiac output. This is in turn due to the combination of increased blood viscosity and loss of hypoxic vasodilatation. Both these factors, however, cannot account completely for the rise in vascular resistance, and therefore the possibility of a direct and/or hormonally-mediated vasopressor effect of rHuEpo has recently been raised. Moreover, scarce information exists on the possible involvement of endogenous erythropoietin in the pathogenesis of arterial hypertension and haematological disturbances observed in primary and some secondary forms of hypertension.
 ...
PMID:Erythropoietin and hypertension. 775 79

Epoetin (recombinant human erythropoietin) is now a widely available though expensive treatment for the anaemia of chronic renal failure, and is effective in more than 95% of patients. Complications of epoetin in this context include hypertension in a third of cases, including hypertensive encephalopathy in a few, and thrombosis of shunts or vascular access devices. Fears that epoetin would cause progression of renal failure have not generally been confirmed, but hyperkalaemia may be a problem in the initial phase of treatment. Epoetin is up to twice as effective when administered subcutaneously rather than intravenously. Responding patients will normally do so within 3 months of starting epoetin. Failures to respond are usually due to iron deficiency or intercurrent disease. Other diseases associated with anaemia and an inappropriately low serum epoetin level include prematurity, the anaemia of cancer and rheumatoid arthritis. The baseline serum endogenous erythropoietin may provide a guide to response in some of these cases. Some encouraging results are being published. Situations where the serum erythropoietin levels are normal or elevated where epoetin has been employed include boosting of haematocrit presurgery as an adjunct to autologous blood donation, treatment of anaemic patients with myelodysplastic syndromes, and improvement of athletic performances.
 ...
PMID:Controversies in selection of epoetin dosages. Issues and answers. 778 87

Erythropoietin therapy for uraemic anaemia is associated with a high rate of hypertensive and thrombotic complications. The mechanism is unknown, but a change in cellular calcium control may be relevant to changes in blood pressure and thrombosis. Platelets were utilized as a model of vascular smooth muscle cells. The effects of erythropoietin therapy on platelet cellular calcium, assessed by fura-2, were measured in 25 patients receiving renal replacement therapy during a 6-month treatment period. Three patients failed to reach a target haemoglobin and were excluded from the analysis. Blood pressure increased in 11 of the remaining 22 subjects, eight requiring an increase in antihypertensive medication. There were no differences in cellular calcium control between the group in whom blood pressure rose and patients with stable blood pressure. Overall there was a fall of 24% in resting cytosolic calcium (baseline 69.2 +/- 5.1 to 52.5 +/- 3.0 nmol/l, P < 0.05) after 3 months of erythropoietin therapy. There was no change in the thrombin-stimulated peak response in the presence of extracellular calcium during therapy, although thrombin-stimulated intracellular release also fell at 3 months (baseline 769 +/- 61 versus 3 months 559 +/- 49 nmol/l, P < 0.01). This study suggests that intracellular free calcium control within platelets improves in response to erythropoietin therapy. However these changes appear not to be related to the development of hypertension.
 ...
PMID:Modulation of platelet cytosolic calcium during erythropoietin therapy in uraemia. 780 Feb 9

A young female presented with hypertension and oliguric renal insufficiency caused by fibromuscular dysplasia of the renal arteries. There was a left kidney remnant and a normal-sized right kidney with a retrograde blood supply through capsular arteries. Reconstruction of the occluded right renal artery with autotransplantation of the kidney after 60 days of oliguric renal insufficiency was followed by complete functional repair. Erythropoietin treatment was a great help in the management of this patient who refused blood transfusions because she was a Jehovah's Witness.
 ...
PMID:Successful renal autotransplantation for renal failure with prolonged oliguria in a Jehovah's Witness with fibromuscular dysplasia of the renal arteries. 783 Aug 49

Erythropoietin has been shown to be effective both in the reversal of anaemia in patients with end-stage renal failure and to increase the volume of autologous red blood cells donated preoperatively as well as to decrease the units of homologous blood transfused. This review analyzes the side effects of erythropoietin reported in the literature for long-term administration (mainly in patients with end-stage renal failure) as well as for acute/short-term administration (in patients participating in an autologous predeposit programme). The most important adverse events reported for long-term administration are as follows: (a) arterial hypertension; (b) cerebral convulsion/hypertensive encephalopathy; (c) thrombo-embolism; (d) iron deficiency; (e) influenza-like syndrome. The numbers given for these side effects are mainly taken from the first and dose-finding studies in patients with renal failure. These figures differ very much from the data given in controlled studies analyzing adverse events as well. Summarizing the results from controlled, multi-center trials in patients with end-stage renal failure or in AIDS patients, no significant differences have been observed between the control group and the patients treated with erythropoietin. The overall-incidence of side effects occurring in either group of these two studies was of approximately 83% and 95%, respectively. In contrast to these results the data published for the dose finding/treatment studies is approximately 30% for development of arterial hypertension, approximately 5% for occurrence of cerebral convulsion/hypertensive encephalopathy, approximately 10% for thrombo-embolic complications/clotting of vascular access, approximately 50% for development of iron deficiency, and approximately 10% for symptoms summarized as influenza-like syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Adverse events of erythropoietin in long-term and in acute/short-term treatment. 795 Jan 71

We examined the hypothesis that administering epoetin to maintain a lower target haemoglobin (Hb) results in a reduced side effect profile and a lower maintenance epoetin dose. We report a prospective study of 14 haemodialysis patients assessing epoetin dose efficiency and side effect profile of partially correcting dialysis-associated anaemia. Initial Hb was 6.2 +/- 0.6 g/dl (mean +/- 1 SD). Intravenous epoetin was commenced at 120 IU/kg/week in 3 divided doses and titrated to achieve a target Hb of 8 g/dl. Follow-up was 24 weeks. The final Hb was 8.7 +/- 0.8 g/dl. The peak epoetin dose was 196 +/- 86 IU/kg/week with a maintenance dose of 141 +/- 71 IU/kg/week. Therapy was associated with hypertension--5 patients (32%); seizures--1 patient (6%) (withdrawn from therapy), and temporary iron deficiency--4 patients (35%). Iron deficiency was corrected with oral therapy. There was 1 treatment failure. Comparable conventional regimens use 100-200 IU/kg to maintain the Hb at 10-13 g/dl and have a similar incidence of side effects. We concluded that reducing the target Hb in order to decrease epoetin requirements is not justified as it offers no benefit over conventional Hb targets in terms of dose requirements or side effects.
 ...
PMID:Partial correction of dialysis-associated anaemia does not reduce erythropoietin dose or the incidence of side effects. 834 95

Erythropoietin (EPO)-induced hypertension is a common complication of EPO usage. The hypothesis that erythropoietin is antinatriuretic and that the sodium retention is mediated by intrarenal angiotensin II production was tested. Experiments were performed in Wistar rat kidneys perfused for 60 min in an isolated system. A dose-response curve was performed for EPO at 0, 10, 100, 1,000, and 10,000 mU/mL. EPO administration resulted in a dose-dependent decrease in sodium excretion to a maximum of 50% at the 1,000 mU/mL dose. In a second experiment, kidneys from five groups were perfused: controls, EPO (100 mU/mL), captopril (50 ng/mL), captopril (50 ng/mL) plus EPO (100 mU/mL), and the angiotensin receptor antagonist losartan (1 nM) plus EPO (100 mU/mL). The administration of EPO resulted in an immediate decrease in average sodium excretion (30%) with no change in GFR or other renal function parameters. Pretreatment with captopril or losartan blocked the effect of EPO. Captopril alone had no effect on renal function. A final experiment demonstrated the ability of losartan (10 nM) to block the pressor effects of angiotensin II (0.01, 0.1, and 1 nM). It was concluded that EPO acts within the kidney to cause the production of angiotensin II, which mediates the increased reabsorption of sodium.
 ...
PMID:Erythropoietin-induced antinatriuresis mediated by angiotensin II in perfused kidneys. 850 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>