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)

Anaemia is frequently diagnosed in patients with cancer, and may have a detrimental effect on quality of life (QoL). We previously conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer.[Bokemeyer C, Aapro MS, Courdi A, et al. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer. Eur J Cancer 2004;40:2201-2216.] We report here an update to these guidelines, including literature published through to November 2005. The results of this updated systematic literature review have enabled us to refine our guidelines based on the full body of data currently available. Level I evidence exists for a positive impact of erythropoietic proteins on haemoglobin (Hb) levels when administered to patients with chemotherapy-induced anaemia or anaemia of chronic disease, when used to prevent cancer anaemia, and in patients undergoing cancer surgery. The addition of further Level I studies confirms our recommendation that in cancer patients receiving chemotherapy and/or radiotherapy, treatment with erythropoietic proteins should be initiated at a Hb level of 9-11 g/dL based on anaemia-related symptoms rather than a fixed Hb concentration. Early intervention with erythropoietic proteins may be considered in asymptomatic anaemic patients with Hb levels 11.9 g/dL provided that individual factors like intensity and expected duration of chemotherapy are considered. Patients whose Hb level is below 9 g/dL should primarily be evaluated for need of transfusions potentially followed by the application of erythropoietic proteins. We do not recommend the prophylactic use of erythropoietic proteins to prevent anaemia in patients undergoing chemotherapy or radiotherapy who have normal Hb levels at the start of treatment, as the literature has not shown a benefit with this approach. The addition of further supporting studies confirms our recommendation that the target Hb concentration following treatment with erythropoietic proteins should be 12-13 g/dL. Once this level is achieved, maintenance doses should be titrated individually. There is Level I evidence that dosing of erythropoietic proteins less frequently than three times per week is efficacious when used to treat chemotherapy-induced anaemia or prevent cancer anaemia, with studies supporting the use of epoetin alfa and epoetin beta weekly and darbepoetin alfa given every week or every 3 weeks. We do not recommend the use of higher than standard initial doses of erythropoietic proteins with the aim of producing higher haematological responses, due to the limited body of evidence available. There is Level I evidence that, within reasonable limits of body weight, fixed doses of erythropoietic proteins can be used to treat patients with chemotherapy-induced anaemia. This analysis confirms that there are no baseline predictive factors of response to erythropoietic proteins that can be routinely used in clinical practice if functional iron deficiency or vitamin deficiency is ruled out; a low serum erythropoietin (EPO) level (only in haematological malignancies) appears to be the only predictive factor to be verified in Level I studies. Further studies are needed to investigate the value of hepcidin, c-reactive protein, and other measures as predictive factors. In these updated guidelines, we explored a new question of whether oral or intravenous iron supplementation increases the response rate to erythropoietic proteins. We found no evidence of increased response with the addition of oral iron supplementation, but there is Level II evidence of improved response to erythropoietic proteins with the addition of intravenous iron. However, the doses and schedules for intravenous iron supplementation are not yet well defined, and further studies in this area are warranted. The two major goals of erythropoietic protein therapy are prevention or elimination of transfusions and improvement of QoL. The total body of evidence shows that red blood cell (RBC) transfusion requirements are reduced following treatment with erythropoietic proteins. This analysis also confirms that QoL is significantly improved in patients with chemotherapy-induced anaemia and in those with anaemia of chronic disease following erythropoietic protein therapy, with more robust evidence now available that QoL was improved in studies investigating early intervention in cases of chemotherapy- or radiotherapy-induced anaemia. There is only indirect evidence that patients with chemotherapy-induced anaemia or anaemia of chronic disease initially classified as non-responders to standard doses proceed to respond to treatment following a dose increase. None of the studies addressed the question in a prospective, randomised fashion, and so the Taskforce does not recommend dose escalation as a general approach in all patients who are not responding. There is still insufficient data to determine the effect on survival following treatment with erythropoietic proteins in conjunction with chemotherapy or radiotherapy. Our analysis of survival endpoints in studies involving patients receiving radio(chemo)therapy found that most studies were inconclusive, with no clear link between the use of erythropoietic proteins and survival. Likewise, we found no clear link between erythropoietic therapy and other endpoints such as local tumour control, time to progression, and progression-free survival. There is no evidence that pure red cell aplasia occurs in cancer patients following treatment with erythropoietic proteins, and the fear of this condition developing should not lead to erythropoietic proteins being withheld in patients with cancer. There is Level I evidence that the risk of thromboembolic events and hypertension are slightly elevated in patients with chemotherapy-induced anaemia receiving erythropoietic proteins. Additional trials are warranted, especially to define the optimal doses and schedules of intravenous iron supplementation during erythropoietic therapy. While our review did not address cost benefit evaluations in detail, the consensus is that studies taking into account all real determinants of cost and benefit need to be performed prospectively.
 ...
PMID:EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. 1718 41

Erythropoietin (EPO) fosters tissue oxygenation by stimulating erythropoiesis. More recently, EPO has been recognized as a tissue-protective cytokine. In this study, we tested the hypothesis that endothelial NO synthase (eNOS) plays a key role in the vascular protective effect of EPO. A murine model of wire-induced injury of carotid artery was used to examine the effect of EPO on endothelial repair and arterial wall architecture. Recombinant human EPO (1000 U/kg, SC, biweekly) was administered for 2 weeks in wild-type and eNOS-deficient mice after which reactivity of isolated carotid arteries was studied in vitro, and the vasculature was histologically assessed. Injured arteries exhibited impairment of endothelium-dependent relaxations to acetylcholine (P<0.05). This was associated with increased medial cross-sectional area (P<0.05). EPO upregulated expression of phosphorylated Ser1177-eNOS and normalized the vasodilator response to acetylcholine (P<0.05). Furthermore, EPO prevented the injury-induced increase in medial cross-sectional area (P<0.05). The vascular protective effects of EPO were abolished in eNOS-deficient mice. Most notably, EPO significantly increased systolic blood pressure and enhanced medial thickening of injured carotid arteries in eNOS-deficient mice (P<0.05). Our results demonstrate that EPO prevents aberrant remodeling of the injured carotid artery. The protective effects of EPO are critically dependent on activation of eNOS.
Hypertension 2007 May
PMID:Essential role of endothelial nitric oxide synthase in vascular effects of erythropoietin. 1737 34

Patients with autonomic failure provide a unique opportunity to study the role of sympathetic function on the regulation of blood volume. These patients have a reversal of the normal diurnal variation in urine output and have twice as much natriuresis during the night. Autonomic failure patients are also unable to conserve sodium and fail to decrease natriuresis in response to dietary sodium restriction. Whereas normal subjects are able to maintain blood pressure within narrow values throughout a wide range of plasma volumes, blood pressure is linearly correlated to changes in plasma volume in autonomic failure patients. Fludrocortisone is often used to increase plasma volume in these patients, but this effect is only transient; its long-term effectiveness probably is due to potentiation of the pressor effects of norepinephrine. On the other hand, epoetin-alpha is effective in correcting the mild anemia that autonomic failure patients commonly have and improves their orthostatic hypotension in part by increasing intravascular volume. Autonomic failure patients, therefore, illustrate the role the sympathetic nervous system has in the regulation of sodium and volume. Conversely, a high salt diet induces sympathoinhibition in normal subjects. Paradoxically, sympathetic activity is increased in patients with salt-sensitive hypertension and contributes to their increase in blood pressure. Thus, in both these conditions the feedback mechanisms involving the sympathetic nervous system and volume homeostasis are impaired.
 ...
PMID:The sympathetic nervous system and blood volume regulation: lessons from autonomic failure patients. 1763 May 95

Patients with ESRD consume a vastly disproportionate amount of financial and human resources. Approximately 0.03% of the US population began renal replacement therapy in 2004, an adjusted incidence rate of 339 per million. Declining incidence rates were observed for most primary causes of ESRD and in most major demographic categories; the worry is that rates of diabetic ESRD continue to rise in younger black adults. Although diabetes and hypertension remain the most commonly reported cause of ESRD, rates of end-stage atherosclerotic renovascular disease seem to be on the rise in older patients. Although clinical care indicators, such as the proportion of hemodialysis patients using fistulas, continue to improve gradually, the proportion of patients overshooting target hemoglobin levels under epoetin therapy may be a source of concern. Survival probabilities have improved steadily in the US ESRD population since the late 1980s, which is remarkable when one considers the ever-expanding burden of comorbidity in incident patients. However, although first-year dialysis mortality rates have clearly improved since 1987, meaningful improvements do not seem to have accrued since 1993, in contrast to steady annual improvements in years 2 through 5. Although most of these findings are grounds for cautious optimism, the same cannot be said for issues of cost; reflecting the growth in the size of the ESRD population, associated costs grew by 57% between 1999 and 2004 and now account for 6.7% of total Medicare expenditures.
 ...
PMID:End-stage renal disease in the United States: an update from the United States Renal Data System. 1765 72

Erythropoietin (EPO) has been used clinically both as an erythropoietic stimulating agent in the treatment of anemia and as a tissue-protective agent in diverse clinical settings including stroke, multiple sclerosis, acute myocardial infarction and others. However, use of EPO or EPO-analogues leads to simultaneous targeting of both the erythropoietic and tissue-protective properties of EPO, and this strategy has been associated with several problems. Specifically, the benefit of correction of cancer-related anemia can be offset by the tissue-protective effects of EPO, which may lead to stimulation of cancer cell proliferation. Conversely, the benefit of tissue-protection in patients with stroke or myocardial infarction can be offset by adverse effects associated with the erythropoietic effects of EPO such as elevation of red blood cell mass, hypertension and prothrombotic phenomena. The finding that the erythropoietic and tissue-protective properties of EPO are conferred via two distinct receptor systems raises the interesting possibility of discovering novel drugs that selectively stimulate either the erythropoietic or the tissue-protective activities of EPO. This article reviews the current status of the clinical use of EPO and EPO-analogues in the treatment of cancer-related anemia and for tissue protection, outlines the distinct molecular biology of the tissue-protective and erythropoietic effects of EPO and discusses strategies of selective targeting of these activities with the goal of exploiting the full therapeutic potential of EPO.
 ...
PMID:Selective modulation of the erythropoietic and tissue-protective effects of erythropoietin: time to reach the full therapeutic potential of erythropoietin. 1768 68

Erythropoietin (EPO) mobilises endothelial progenitor cells and promotes neovascularisation in heart failure. The present authors studied the effects of EPO on pulmonary vascular and cardiac remodelling in a model for flow-associated pulmonary arterial hypertension (PAH). PAH was induced in adult male Wistar rats by the injection of monocrotaline combined with an abdominal aortocaval shunt 1 week later (PAH or experimental group). Immediately afterwards, rats were randomised into those who received treatment with EPO (PAH+EPO group) and controls. Pulmonary and systemic haemodynamics, and right ventricular and pulmonary vascular remodelling were evaluated 3 weeks later. Vascular occlusion of the intra-acinar pulmonary vessels (13.4+/-0.7 versus 16.7+/-1.3% in PAH+EPO and PAH, respectively) and medial wall thickness of the pre-acinar arteries (wall-to-lumen ratio 0.13+/-0.01 versus 0.17+/-0.01 in PAH+EPO and PAH, respectively) decreased after treatment with EPO. Moreover, right ventricular capillary density was increased by therapy (2,322+/-61 versus 2,100+/-63 capillaries x mm(-2) in PAH+EPO and PAH, respectively). Increased mean pulmonary arterial pressure and decreased right ventricular contractility in the model were not altered by EPO treatment. In this rat model of flow-associated pulmonary arterial hypertension, erythropoietin treatment beneficially affected pulmonary vascular and cardiac remodelling. These histopathological effects were not accompanied by significantly improved haemodynamics.
 ...
PMID:Effects of erythropoietin on advanced pulmonary vascular remodelling. 1789 19

Anaemia is a frequent complication in cancer patients and may be multifactorial in origin. Treatment with recombinant human erythropoietin (rHuEPO) is an alternative to red blood cell transfusion. The evidence from clinical trials has established that patients with chemotherapy-induced anaemia with a haemoglobin concentration below 10 g/dl benefit from epoetin therapy. The native glycoprotein hormone consists of 165 amino acids with three N-glycosylation and one O-glycosylation sites. Epoetin and darbepoetin bind to the EPO receptor to induce intracellular signalling by the same intracellular molecules as native EPO. There are some differences in the glycosylation pattern which lead to variations in the pharmacokinetics and pharmacodynamics profiles. Pharmacokinetic and therapeutic studies have examined the use of rHuEPO administered intravenously and subcutaneously and there is accumulating evidence that the latter route has several advantages in cancer patients. After subcutaneous administration, the bioavailability of epoetin is about 20-30% and has a plasma half-life of >24 h. Darbepoetin has a longer half-life after subcutaneous administration of 48 h. The general recommendations are based on evidence from trials in which epoetin was administered 150 U/kg thrice weekly. The recommended initial dose for darbepoetin alpha is 2.25 mug/kg per week. The most serious adverse effects are hypertension, bleeding and increased risk of thrombotic complications. Caution is advised when used in patients who are at high risk for thromboembolic events. In the management of anaemic cancer patients, physicians should closely follow the National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) guidelines.
 ...
PMID:Erythropoietin pharmacology. 1805 26

Pregnancy in women on hemodialysis is very uncommon, and rates of spontaneous abortion, hypertension, pre-eclampsia, polyhydramnios, pre-term labor, and premature birth are high. This article documents a successful 39-week pregnancy in a woman who conceived at Stage 5 in chronic kidney disease and who started hemodialysis at 7 weeks gestation. The dialysis prescription included 3-hour treatments 5 times weekly. Blood urea nitrogen levels and fluid removal by ultrafiltration were managed according to the recommendations in the available literature. Erythropoietin and IV iron were utilized liberally for her worsening anemia. She was closely monitored by a multidisciplinary team at the dialysis center and by the perinatologist in her health care system. Pre-term labor and premature birth were avoided; however, she developed hypertension, pre-eclampsia, and polyhydramnios. She delivered a healthy female by scheduled cesarean section. There is limited data on management of this minority population, and much can be learned regarding mineral metabolism, safety and use of medications, control of hypoalbuminemia, and care practices to reduce the incidence of maternal complications and premature birth.
 ...
PMID:A successful 39-week pregnancy on hemodialysis: a case report. 1878 97

This review summarizes the evidence for a hypertensinogenic effect of Erythropoietin (Epo) in normal human subjects and predialysis, hemodialysis, and continuous ambulatory peritoneal dialysis (CAPD) patients. The possible mechanisms of Epo-induced hypertension are examined with in vivo animal and in vitro data, as well as pathophysiological human studies in both normal subjects and CKD patients. The evidence for a hypertensinogenic effect of erythropoiesis-stimulating agents (ESAs) in normal subjects, predialysis CKD, hemodialysis, and CAPD patients is compelling. Epo increases BP directly and notably independently of its erythropoietic effect and its effect on blood rheology. The potential for the development of future agents that might act as specific stimulators of erythropoiesis, devoid of direct hemodynamic side effects is underscored.
 ...
PMID:Arterial hypertension induced by erythropoietin and erythropoiesis-stimulating agents (ESA). 1921 74

An additional target for reducing infarct size, namely, attenuation of apoptosis, has recently emerged. Erythropoietin (Epo) exhibits properties that may attenuate this process and enhance neovascularization, thereby preserving jeopardized myocardium. Potentially adverse effects of Epo, including hypertension, thrombosis and possible exacerbation of occult neoplasms can likely be averted with analogues such as carbamylated and asialo Epo, which are devoid of erythropoietic effects, yet retain tissue-protective characteristics. With a single, but adequate dose of Epo administered early after the onset of acute myocardial infarction, coupled with therapy to induce reperfusion, tissue protection conferred by Epo and its analogues may facilitate the preservation of myocardium subjected to ischemic insults, thereby improving prognosis.
 ...
PMID:Heart disease and erythropoietin. 1980 72


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