losartan-potassium and Seizures

The aim of this meta-analysis was to review the scientific literature published until April 18, 2021, to summarize existing knowledge on the efficacy and safety of erythropoietin (EPO) for traumatic brain injury (TBI).. This systematic review followed PRISMA guidelines. Randomized controlled trials (RCTs) reporting on the efficacy and safety of EPO in the treatment of TBI were systematically searched in relevant electronic databases according to a pre-designed search strategy. The primary outcomes are the mortality; and secondary outcomes are the good functional outcome (GFO) and adverse events (AEs).. A total of 10 RCTs involving 2,402 participants fulfilled the inclusion criteria. The results showed that there is a significant difference in terms of the mortality (RR = 0.67, 95% CI = 0.54-0.84, P = 0.0003) and seizure rate (RR = 0.52, 95% CI = 0.29-0.96, P = 0.04) between the EPO groups compared to those in the control groups. However, compared with the control groups, the GFO in the EPO groups was not statistically significant (RR = 1.18, 95% CI = 0.93-1.48, P = 0.17).. Findings of the present meta-analysis suggest that the use of EPO could reduce mortality rate in patients with TBI, without increasing the incidence of AEs. EPO has potential research and application value in the treatment of TBI.

Topics: Brain Injuries, Traumatic; Erythropoietin; Humans; Incidence; Seizures

Advances in the care of high-risk newborn babies have contributed to reduced mortality rates for premature and term births, but the surviving neonates often have increased neurological morbidity. Therapies aimed at reducing the neurological sequelae of birth asphyxia at term have brought hypothermia treatment into the realm of standard care. However, this therapy does not provide complete protection from neurological complications and a need to develop adjunctive therapies for improved neurological outcomes remains. In addition, the care of neurologically impaired neonates, regardless of their gestational age, clearly requires a focused approach to avoid further injury to the brain and to optimize the neurodevelopmental status of the newborn baby at discharge from hospital. This focused approach includes, but is not limited to, monitoring of the patient's brain with amplitude-integrated and continuous video EEG, prevention of infection, developmentally appropriate care, and family support. Provision of dedicated neurocritical care to newborn babies requires a collaborative effort between neonatologists and neurologists, training in neonatal neurology for nurses and future generations of care providers, and the recognition that common neonatal medical problems and intensive care have an effect on the developing brain.

Topics: Anesthetics, Inhalation; Anticonvulsants; Antioxidants; Asphyxia Neonatorum; Electroencephalography; Erythropoietin; Humans; Hypothermia, Induced; Infant, Newborn; Intensive Care, Neonatal; Monitoring, Physiologic; Nervous System Diseases; Neuroprotective Agents; Seizures; Xenon

Anaemia is a frequent complication of cancer. Recently, some concerns have appeared regarding the safety of erythropoiesis-stimulating agents (ESAs) for the treatment of anaemia in cancer patients. The current review will analyse the main arguments in favour of erythropoietin (EPO), as well as those against EPO in chemotherapy-induced anaemia and in cancer-related anaemia. The principal concerns are tumour progression, increased mortality and the risk of venous thromboembolic events (VTEs). Recent meta-analyses have come to divergent conclusions.. Several meta-analyses have reviewed the data regarding VTEs, EPO receptors on tumours and tumour progression as well as mortality.. As of now, ESAs should only be used within the indications as given in the various guidelines.

Topics: Anemia; Disease Progression; Erythropoietin; Hematinics; Humans; Hypertension; Neoplasms; Red-Cell Aplasia, Pure; Risk Assessment; Seizures

Perinatal hypoxic-ischemic encephalopathy can be a devastating complication of childbirth. Herein, the authors review the pathophysiology of hypoxic-ischemic encephalopathy and the current status of neuroprotective strategies to ameliorate the injury centering on four themes: (1) monitoring in the perinatal period, (2) rapid identification of affected neonates to allow timely institution of therapy, (3) preconditioning therapy (a therapeutic that reduces the brain vulnerability) before hypoxic-ischemic encephalopathy, and (4) prompt institution of postinsult therapies to ameliorate the evolving injury. Recent clinical trials have demonstrated the significant benefit for hypothermic therapy in the postnatal period; furthermore, there is accumulating preclinical evidence that adjunctive therapies can enhance hypothermic neuroprotection. Advances in the understanding of preconditioning may lead to the administration of neuroprotective agents earlier during childbirth. Although most of these neuroprotective strategies have not yet entered clinical practice, there is a significant hope that further developments will enhance hypothermic neuroprotection.

Topics: Adrenergic alpha-Agonists; Animals; Anti-Inflammatory Agents; Anticonvulsants; Antioxidants; Apoptosis; Erythropoietin; Female; Free Radical Scavengers; Humans; Hyperoxia; Hypocapnia; Hypoxia-Ischemia, Brain; Inflammation; Ischemic Preconditioning; Neuroprotective Agents; Neurotoxins; Pregnancy; Prenatal Diagnosis; Receptors, N-Methyl-D-Aspartate; Seizures

Topics: Adrenal Cortex Hormones; Angioedema; Blood Component Transfusion; Brain Edema; Cyclosporins; Endothelium, Vascular; Erythropoietin; Humans; Hypertensive Encephalopathy; Immunosuppressive Agents; Magnetic Resonance Imaging; Seizures; Syndrome

Erythropoietin (EPO) is a glycoprotein that has been shown to mediate response to hypoxia, and is most notably recognized for its central role in erythropoiesis. In a series of experiments using rodent models, the ability of systemically administered recombinant human erythropoietin (r-HuEPO, epoetin alfa) to cross the blood-brain barrier and affect the outcome of neuronal injury or cognitive function was evaluated. It was shown that EPO and EPO receptors are expressed at capillaries of the brain-periphery interface, and that systemically administered epoetin alfa crossed the blood-brain barrier. Compared with control animals, epoetin alfa significantly reduced tissue damage in an ischemic stroke model when administered 24 hours before inducing stroke, with significant protection still evident when epoetin alfa was administered 6 hours poststroke. Epoetin alfa reduced injury by blunt trauma when administered 24 hours before trauma, with a significantly smaller volume of tissue necrosis noted when compared with controls. The observation that epoetin alfa may reduce nervous system inflammation was confirmed when an experimental autoimmune encephalomyelitis model in which rats were shown to have significantly delayed onset and reduced severity of experimental autoimmune encephalomyelitis symptoms after treatment with epoetin alfa. Epoetin alfa also was shown to ameliorate the latency and severity of seizures, and significantly increase survival versus controls when exposed to kainate. These findings suggest future potential therapeutic uses for epoetin alfa beyond its current use to increase erythropoiesis.

Topics: Animals; Blood-Brain Barrier; Brain; Brain Ischemia; Central Nervous System; Encephalomyelitis; Epoetin Alfa; Erythropoietin; Humans; Kainic Acid; Mice; Models, Animal; Neuroprotective Agents; Receptors, Erythropoietin; Recombinant Proteins; Seizures

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)

Topics: Blood Transfusion, Autologous; Cardiovascular Diseases; Erythropoietin; Humans; Seizures; Thromboembolism; Time Factors

Anemia is one of the major limitations to rehabilitation in patients with end-stage renal disease (ESRD). The efficacy of recombinant human erythropoietin (rHuEPO) in the treatment of renal anemia is well established. Nevertheless, rHuEPO therapy has been associated with serious untoward effects. There appears to be an increased risk of hypertension, not infrequently accompanied by hypertensive encephalopathy and seizures. The mechanism of hypertension remains uncertain. It is associated with an increase in blood viscosity, a reversal of hypoxic vasodilatation, and possibly, a direct pressor effect of the hormone. Seizures, otherwise, may be the result of cerebral hypoperfusion and, finally, of a focal cerebral edema. The guidelines for rHuEPO treatment and prevention of associated convulsions are outlined. The possible convulsive risk induced by this treatment, even at low doses, particularly in patients with a previous history of seizures, is stressed.

Topics: Anemia; Erythropoietin; Humans; Hypertension; Recombinant Proteins; Renal Dialysis; Seizures

Topics: Anemia; Erythropoietin; Humans; Hypertension; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Quality of Life; Renal Dialysis; Seizures; Thrombosis

Fifty-five hemodialysis patients (pts) received rHuEpo for 3-5 years (51 +/- 11 months, hematocrit 32.5 +/- 3.7). BP medication was required in 42% of pts prior to rHuEpo (Hct 20.8 +/- 3.5) and 69% (38 patients) now require such therapy. BP was controlled with single therapy in 16 pts and only 8 required 3 or more different BP drugs. Vascular access clotting episodes were rare in pts with autologous fistula (17 of 24 pts had no clotting), whereas access clotting episodes were 10 times more common in pts with AV grafts, yet 20% had no clotting after 3-5 years of rHuEpo. Heart size decreased in most who initially had cardiomegaly. Cardiovascular related and other deaths were decreased in this selected group when compared to other dialysis pts matched for age, race and type of renal disease.

Topics: Anemia; Blood Coagulation; Cardiovascular System; Erythropoietin; Humans; Hypertension; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Seizures; Time Factors

Recombinant erythropoietin is usually associated with marked improvement in physiological and psychological well-being. Adverse effects are unusual. In this report, the unusual occurrence of seizures, increased clotting, and influenza-like syndromes is reviewed. Emphasis is given to adverse effects noted in the few available placebo-controlled studies.

Topics: Anemia; Blood Coagulation Disorders; Clinical Trials as Topic; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins; Seizures

Topics: Anemia; Anemia, Hypochromic; Animals; Drug Hypersensitivity; Erythropoietin; Humans; Hyperkalemia; Hypertension; Peritoneal Dialysis, Continuous Ambulatory; Phosphates; Recombinant Proteins; Renal Dialysis; Seizures; Thrombosis; Uremia

Topics: Adult; Aged; Erythropoietin; Female; Hemodynamics; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Seizures

An ancillary study of the High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial for neonates with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia examined the hypothesis that neonates randomized to receive erythropoietin (Epo) would have a lower seizure risk and burden compared with neonates who received placebo.. Electroencephalograms (EEGs) from 7/17 HEAL trial centers were reviewed. Seizure presence was compared across treatment groups using a logistic regression model adjusting for treatment, HIE severity, center, and seizure burden prior to the first dose. Among neonates with seizures, differences across treatment groups in median maximal hourly seizure burden were assessed using adjusted quantile regression models.. Forty-six of 150 (31%) neonates had EEG seizures (31% in Epo vs 30% in placebo, p = 0.96). Maximal hourly seizure burden after the study drug was not significantly different between groups (median 11.4 for Epo, IQR: 5.6, 18.1 vs median 9.7, IQR: 4.9, 21.0 min/h for placebo).. In neonates with HIE treated with hypothermia who were randomized to Epo or placebo, we found no meaningful between-group difference in seizure risk or burden. These findings are consistent with overall trial results, which do not support Epo use for neonates with HIE undergoing therapeutic hypothermia.. In the HEAL trial of erythropoietin (Epo) vs placebo for neonates with encephalopathy presumed due to hypoxic-ischemic encephalopathy (HIE) who were also treated with therapeutic hypothermia, electrographic seizures were detected in 31%, which is lower than most prior studies. Epo did not reduce the proportion of neonates with acute provoked seizures (31% in Epo vs 30% in placebo) or maximal hourly seizure burden after the study drug (median 11.4, IQR 5.6, 18.1 for Epo vs median 9.7, IQR 4.9, 21.0 min/h for placebo). There was no anti- or pro-convulsant effect of Epo when combined with therapeutic hypothermia for HIE.

Topics: Asphyxia; Erythropoietin; Humans; Hypothermia; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Seizures

Topics: Anemia; Blood Coagulation; Blood Pressure; Erythropoietin; Humans; Iron; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Seizures

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.

Topics: Anemia; Anemia, Hypochromic; Blood Pressure; Clinical Trials as Topic; Drug Evaluation; Erythropoietin; Hematocrit; Humans; Hypertension; Kidney Failure, Chronic; Monitoring, Physiologic; Recombinant Proteins; Renal Dialysis; Seizures

Topics: Anemia; Erythropoietin; Humans; Hypertension; Iron; Kidney Failure, Chronic; Multicenter Studies as Topic; Renal Dialysis; Seizures; United States

Topics: Anemia; Arteriovenous Shunt, Surgical; Erythropoietin; Humans; Hypertension; Kidney Failure, Chronic; Multicenter Studies as Topic; Neoplasms; Renal Dialysis; Seizures; Thrombocytosis; Thrombosis

Topics: Adolescent; Adult; Anemia; Child; Child, Preschool; Erythrocyte Count; Erythropoietin; Female; Ferritins; Growth; Hematocrit; Humans; Hypertension; Kidney Failure, Chronic; Male; Multicenter Studies as Topic; Reticulocytes; Seizures; Thrombosis

This case demonstrates an underrecognized cause of posterior reversible encephalopathy syndrome (PRES).. We report a 51-year-old male with a history of essential hypertension without preexisting renal impairment who presented with 3 days of occipital headache and convulsive status epilepticus in the setting of refractory hypertension. He had been receiving outpatient human recombinant erythropoietin injections for virally mediated bone marrow suppression, which worsened his baseline hypertension. Magnetic resosnance imaging (MRI) of the brain on admission showed diffuse bilateral, symmetric signal hyperintensities and patchy enhancement involving the cortex and white matter in both cerebral hemispheres. His blood pressure and seizures were successfully treated during hospital admission, with complete resolution of his neurological deficits. MRI brain performed 6 weeks from initial scan showed normalization of his prior findings.. Recombinant human erythropoietin (RhEPO) may be an underrecognized cause of PRES and should be considered in patients receiving this treatment regardless of the absence or presence of renal impairment. RhEPO-mediated precipitation/exacerbation of hypertension, alterations in cerebral blood flow, and changes in endothelial integrity may underlie this association. MRI signal changes are reversible and typical for that of PRES, and significant improvement of symptoms can be expected.

Topics: Brain; Erythropoietin; Humans; Hypertension; Male; Middle Aged; Posterior Leukoencephalopathy Syndrome; Seizures

Topics: Cerebral Palsy; Child, Preschool; Epilepsy; Erythropoietin; Female; Humans; Infant; Male; Recombinant Proteins; Seizures

Although it is accepted that prolonged and repeated seizures can cause epileptogenesis, memory deficits and neuronal death, the precise relation between epileptic seizures and neuronal death remains unclear. Erythropoietin (EPO) exhibits neuroprotective and anti-epileptic effects. We investigated the effect of a single pentylentetrazole (PTZ) induced tonic-clonic seizure on the pyramidal neurons of the cornu ammonis 1 (CA1) and CA3 regions of hippocampus. We also investigated the effects of EPO on seizure, memory and on brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase-B, sirtuin-1 (SIRT1), which are important for memory. Forty male rats were divided into four groups: control, saline treated, single 60 mg/kg dose PTZ treated, 3000 IU/kg EPO treated, and 3000 IU/kg EPO treated 24 h before PTZ administration. Seizure latency and severity were assessed following PTZ injection. A passive avoidance test was performed 24 h after seizure. BDNF, TrkB and SIRT1 levels were measured in serum, hippocampus and cortex. The hippocampus was examined histologically, and neuronal nuclear antigen (NeuN) was investigated using immunohistochemistry. EPO pretreatment decreased seizure severity and prolonged seizure latency. Single dose PTZ-induced seizures did not affect memory. Numbers of cells in the CA1 region did not change, although the number of dark stained neuron increased. Both total cell numbers and percentage of dark stained cells were elevated in the CA3 region following PTZ induced seizures. EPO pretreatment decreased the number of dark cells in both CA1 and CA3 regions and the number of cells in the CA3 region. NeuN labeling was unchanged in the CA1 and CA3 regions in the PTZ group; however, EPO pretreatment increased NeuN labeling in the CA3 region. Although EPO exhibited an anticonvulsive effect, single dose EPO pretreatment did not affect memory in either animals not exposed to PTZ or animals that had been subjected to PTZ-induced seizures. EPO pretreatment prolonged seizure latency and reduced seizure severity after PTZ-induced seizures. The anti-seizure and neuroprotective effects of EPO pretreatment may be due to the protection of CA1 and CA3 neurons, possibly owing to SIRT1 and BDNF activity.

Topics: Animals; Disease Models, Animal; Erythropoietin; Hippocampus; Male; Memory; Neurons; Neuroprotective Agents; Pentylenetetrazole; Rats; Seizures

Recurrent seizures can result in neuronal death, cognitive deficits and intellectual disability, which causes devastating damage in children. Recombinant human erythropoietin (rhEPO) is considered a neuroprotective factor in many nervous system diseases. However, the precise mechanisms through which rhEPO exerts its neuroprotective effects on epilepsy remain unknown. Thus, in this study, we determined whether rhEPO protects against brain injury by inducing cortical neuronal autophagy through blunting the mammalian target of rapamycin complex 1 (mTORC1) pathway in the developing brains of rats with seizures.. We used kainic acid to induce recurrent seizures in rats. Nissl staining and TUNEL analysis were used to evaluate the neuronal damage and apoptotic cells. Western blot analysis was employed to evaluate the phospho-mammalian target of rapamycin (p-mTOR)/mTOR protein ratio, the phospho-ribosomal protein S6 (S6)/S6 protein ratio, the microtubule-associated protein light chain 3 (LC3) II/I protein ratio and sequestosome 1 (P62/SQSTM1) protein expression levels.. rhEPO reversed the decrease in the number of Nissl-positive neurons and the increase in the number of apoptotic cells in the kainic acid group. Notably, rhEPO induced autophagy and inhibited the mTORC1 pathway to protect against brain injury in rats with seizures. Treating rats with rapamycin blocked the mTORC1 pathway and masked the abovementioned effects of rhEPO.. Based on these results, rhEPO protects against brain injury by activating autophagy through blunting the mTORC1 pathway in developing rats with seizures.

Topics: Animals; Autophagy; Brain; Brain Injuries; Epilepsy; Erythropoietin; Humans; Male; Mechanistic Target of Rapamycin Complex 1; Neurons; Neuroprotection; Neuroprotective Agents; Rats, Sprague-Dawley; Recombinant Proteins; Seizures; Signal Transduction

Epilepsy is among the most common neurological disorders. Recurrent seizures result in neuronal death, cognitive deficits and intellectual disabilities in children. Currently, recombinant human erythropoietin (rhEPO) is considered to play a neuroprotective role in nervous system disorders. However, the precise mechanisms through which rhEPO modulates epilepsy remain unknown. Based on results from numerous studies, we hypothesized that rhEPO protects against hippocampal damage in developing rats with seizures probably by modulating autophagy via the ribosomal protein S6 (S6) in a time-dependent manner. First, we observed that rats with recurrent seizures displayed neuronal loss in the hippocampal CA1 region. Second, rhEPO injection reduced neuronal loss and decreased the number of apoptotic cells in the hippocampal CA1 region. Moreover, rhEPO increased the Bcl-2 protein expression levels and decreased the ratio of cleaved caspase-3/caspase-3 in the hippocampus. Finally, rhEPO modulated autophagy in the hippocampus in a time-dependent manner, probably via the S6 protein. In summary, rhEPO protects against hippocampal damage in developing rats with seizures by modulating autophagy in a time-dependent manner, probably via the S6 protein. Consequently, rhEPO is a likely drug candidate that is capable of attenuating brain injury.

Topics: Animals; Autophagy; Brain Injuries; Epilepsy; Erythropoietin; Hippocampus; Humans; Male; Neurons; Neuroprotective Agents; Rats, Sprague-Dawley; Recombinant Proteins; Ribosomal Protein S6 Kinases; Seizures; Time Factors

In the present study, the levels of neuron-specific enolase (NSE), interleukin-1β (IL-1β), and erythropoietin (EPO) in cerebrospinal fluid (CSF) in children with idiopathic epilepsy were measured to illuminate the relationships between these markers with idiopathic epilepsy.. Eighty-five children from 6 months to 12.5 years of age with single, previously undiagnosed, and untreated idiopathic epilepsy were participated in this study. The concentrations of CSF NSE, 1L-1β, and EPO were measured by specific ELISA methods.. The mean concentrations of CSF NSE, IL-1β, and EPO in the epileptic groups showed a significant increase (P < 0.01) compared with those in the control groups. Besides, the mutual correlations of NSE, 1L-1β, and EPO were also analyzed. Results showed that there were positive correlations between the levels of IL-1β, NSE, and EPO.. The changes of NSE, 1L-1β, and EPO level in CSF may be beneficial for the pathophysiology study of epileptic seizures and the identification and diagnosis of a seizure clinically.

Topics: Biomarkers; Case-Control Studies; Child; Child, Preschool; Cross-Sectional Studies; Erythropoietin; Female; Humans; Infant; Interleukin-1beta; Male; Phosphopyruvate Hydratase; Seizures

To perform a feasibility and safety study with recombinant human erythropoietin (rhEPO) in neonates with perinatal arterial ischemic stroke.. Neonates with a magnetic resonance imaging-confirmed perinatal arterial ischemic stroke (n = 21) were treated with 1000 IU/kg rhEPO immediately after diagnosis and at 24 and 48 hours after the first dose. Repeat magnetic resonance imaging was performed when the patients were 3 months of age. Coagulation and hematologic variables (red blood cells, white blood cells, platelet counts) were performed in the first week after initiation of treatment. We also compared 10 patients who were treated with rhEPO with 10 historic infants with perinatal arterial ischemic stroke matched for the involved arterial branch to investigate whether rhEPO reduces the residual size of the infarction and subsequent brain growth between first and second scan.. Seizures were a first symptom in 20 of 21 neonates. Heart rate, blood pressure, and coagulation function were in the normal range, as were red blood cells, white blood cells, and platelet counts. In a subgroup of 10 rhEPO-treated neonates, no differences were detected in residual infarction volumes or neurodevelopmental outcome compared with their historical nontreated counterparts.. rhEPO in neonates with perinatal arterial ischemic stroke had no adverse effects on red blood cells, white blood cells, platelets counts, or coagulation. rhEPO, 3000 IU/kg in total, given during a 3-day period, appears to be a safe therapy. The beneficial effects remains to be demonstrated in a larger, randomized, double-blind, placebo-controlled trial.

Topics: Blood Cell Count; Brain Ischemia; Cerebral Palsy; Erythropoietin; Feasibility Studies; Female; Hematocrit; Hemoglobins; Humans; Infant, Newborn; Magnetic Resonance Imaging; Male; Matched-Pair Analysis; Neuroprotective Agents; Recombinant Proteins; Seizures; Stroke

Erythropoietin (EPO) suppresses epileptic seizures, but the mechanism is unclear. The search for novel targets in the therapy of epilepsy has focused recently on brain inflammation since brain inflammation and the associated blood-brain barrier (BBB) damage appears to be an integral part of epilepsy pathophysiology. We examined the effects of EPO on proinflammatory mediators in brain and serum in PTZ-induced generalized seizure model. The inflammation markers (IL-1β, TNF-α, IL-6, IL-10), BBB and neuron damage markers (S100B, Neuron specific enolase; NSE, respectively) in serum and brain of Sprague-Dawley male rats were examined with the ELISA method. Nitric oxide synthase (NOS) isoforms were investigated immunohistochemically in hippocampus. EPO treatment 4 h and 24 h before PTZ administration had diverse effects. EPO treatment 4 h before PTZ administration elongated the seizure latency, decreased the inflammation and damage markers in serum and brain significantly, whereas EPO treatment 24 h before PTZ administration lowered inflammation and damage markers to control levels and decreased the seizure stage. PTZ-induced seizures increased inducible NOS (iNOS) activity and decreased endothelial NOS (eNOS) activity in hippocampus. Both EPO pretreatments reversed these effects. These findings, i.e., decreased iNOS activity and increased eNOS activity by EPO suggest the first time that the favorable effect of EPO pretreatment on inflammatory mediators triggered by PTZ-induced seizures. This can provide further insight into epilepsy treatment and new prophylactic strategies against epilepsy risk.

Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents; Convulsants; Cytokines; Drug Administration Schedule; Encephalitis; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Hippocampus; Male; Pentylenetetrazole; Phosphopyruvate Hydratase; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein beta Subunit; Seizures; Time Factors

Erythropoietin, a member of the type 1 cytokine superfamily, controls proliferation and differentiation of erythroid progenitor cells through binding to and dimerization of the erythropoietin receptor. Both erythropoietin and its receptor are also expressed in the central nervous system, where they are involved in tissue protection. However, the use of erythropoietin as a neuroprotective agent may be hampered by its erythropoietic activity. Therefore, developing non-haematopoietic erythropoietin mimetics is important. Based on the crystal structure of the complex of erythropoietin and its receptor, we designed a peptide, termed Epotris, corresponding to the C α-helix region (amino-acid residues 92-111) of human erythropoietin. The peptide specifically bound to the erythropoietin receptor and promoted neurite outgrowth and survival of primary neurons with the same efficiency as erythropoietin, but with 10(3)-fold lower potency. Knockdown of the erythropoietin receptor or interference with its downstream signalling inhibited the Epotris-induced neuritogenic and pro-survival effect. Similarly to erythropoietin, Epotris penetrated the blood-brain barrier. Moreover, treatment with the peptide attenuated seizures, decreased mortality and reduced neurodegeneration in an in vivo model of kainic acid-induced neurotoxicity. In contrast to erythropoietin, Epotris did not stimulate erythropoiesis upon chronic administration. Thus, Epotris is a novel neuroprotective non-haematopoietic erythropoietin mimetic that may offer new opportunities for the treatment of neurological disorders.

Topics: Animals; Blood-Brain Barrier; Capillary Permeability; Cells, Cultured; Erythropoiesis; Erythropoietin; Female; Gene Knockdown Techniques; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neurites; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Peptide Fragments; Rats; Rats, Wistar; Receptors, Erythropoietin; Seizures

Brain injury from preterm birth predisposes children to cerebral palsy, epilepsy, cognitive delay, and behavioral abnormalities. The CNS injury often begins before the early birth, which hinders diagnosis and concurrent treatment. Safe, effective postnatal interventions are urgently needed to minimize these chronic neurological deficits. Erythropoietin (EPO) is a pleiotropic neuroprotective cytokine, but the biological basis of its efficacy in the damaged developing brain remains unclear. Coordinated expression of EPO ligand and receptor expression occurs during CNS development to promote neural cell survival. The authors propose that prenatal third trimester global hypoxia-ischemia disrupts the developmentally regulated expression of neural cell EPO signaling, and predisposes neural cells to death. Furthermore, the authors suggest that neonatal exogenous recombinant human EPO (rhEPO) administration can restore the mismatch of EPO ligand and receptor levels, and enhance neural cell survival.. Transient systemic hypoxia-ischemia (TSHI) on embryonic Day 18 in rats mimics human early-third trimester placental insufficiency. This model was used to test the authors' hypothesis using a novel clinically relevant paradigm of prenatal injury on embryonic Day 18, neonatal systemic rhEPO administration initiated 4 days after injury on postnatal Day 1, and histological, biochemical, and functional analyses in neonatal, juvenile, and adult rats.. The results showed that prenatal TSHI upregulates brain EPO receptors, but not EPO ligand. Sustained EPO receptor upregulation was pronounced on oligodendroglial lineage cells and neurons, neural cell populations particularly prone to loss from CNS injury due to preterm birth. Postnatal rhEPO administration after prenatal TSHI minimized histological damage and rescued oligodendrocytes and gamma-aminobutyric acidergic interneurons. Myelin basic protein expression in adult rats after insult was reduced compared with sham controls, but could be restored to near normal levels by neonatal rhEPO treatment. Erythropoietin-treated TSHI rats performed significantly better than their saline-treated peers as adults in motor skills tests, and showed significant seizure threshold restoration using a pentylenetetrazole increasing-dose paradigm.. These data demonstrate that neonatal rhEPO administration in a novel clinically relevant paradigm initiated 4 days after a global prenatal hypoxic-ischemic insult in rats rescues neural cells, and induces lasting histological and functional improvement in adult rats.

Topics: Animals; Blotting, Western; Cell Death; Erythropoietin; Fetal Diseases; Hypoxia-Ischemia, Brain; Immunohistochemistry; Ligands; Motor Skills; Neurons; Oligodendroglia; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; Recombinant Proteins; Seizures

The neuroprotective and trophic actions of erythropoietin (EPO) have been tested in several animal models of insult, injury, and neurodegeneration. Recent studies in human volunteers demonstrated that EPO improves cognition and also elicits antidepressant effects. It is believed that the behavioral effects are mediated by EPO's trophic effect on neuronal systems. We therefore tested whether EPO is able to alter behavior and brain gene expression in rats.. The expression of EPO and EPO receptor (EPOR) in multiple brain regions was examined by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. The regulation of EPO and the transcription factor hypoxia-induced factor-alpha (HIF1alpha) after electroconvulsive seizure (ECS) was investigated. Behavioral effects of EPO were tested in the rodent forced swimming and novelty-induced hypophagia (NIH) models. EPO gene profiles were obtained by microarray analysis of the hippocampus after intracerebroventricular infusion.. EPO and EPOR were widely expressed in the brain albeit at low levels. Highest level of EPO and EPOR were in the choroid plexus and striatum, respectively. Peripheral administration of EPO was sufficient to produce a robust antidepressant-like effect in the forced swim and NIH tests. Gene expression profiles revealed that EPO induces the expression of neurotrophic genes such as brain-derived neurotrophic factor, VGF (nonacronymic), and neuritin.. EPO is induced by ECS and independently exhibits antidepressant-like efficacy in the forced swim and NIH tests. EPO regulates the expression of genes implicated in antidepressant action and appears to be a candidate molecule for further testing in neuropsychiatry.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Brain-Derived Neurotrophic Factor; Depression; Disease Models, Animal; Electroshock; Erythropoietin; Exploratory Behavior; Gene Expression Profiling; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Locomotion; Male; Oligonucleotide Array Sequence Analysis; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; Seizures; Swimming

Adult neural stem cells (NSCs) possess the potentials to self-renew and exert neuroprotection. In this study, we examined whether adult NSCs had anti-epileptic effects in rats with status epilepticus (SE) induced by kainic acid (KA) and whether co-administration of erythropoietin (EPO) enhanced anti-epileptic effects or cell survival. Adult NSCs were transplanted into KA-lesioned hippocampus with or without intracerebroventricular EPO infusion. Electronic encephalography (EEG) was recorded for 3 weeks after transplantation. The frequency of abnormal spikes in rats with NSC transplantation decreased significantly compared to those of rats without NSC transplantation. Most of the transplanted NSCs differentiated into GFAP-positive astrocytes. EPO infusion significantly enhanced the survival of NSCs, but not neuronal differentiation or migration. NSC transplantation increased the number of neuropeptide Y (NPY) and glutamic acid decarboxylase 67 (GAD67)-positive interneurons. NSC transplantation also suppressed mossy fiber sprouting into the inner molecular layer with subsequent reduction of hippocampal excitability, which finally prevented the development of spontaneous recurrent seizures in adult rats after KA-induced SE. This study might shed light on the cytoarchitectural mechanisms of temporal lobe epilepsy as well as clarify the effect of adult NSC transplantation with intracerebroventricular EPO infusion for temporal lobe epilepsy.

Topics: Action Potentials; Adult Stem Cells; Analysis of Variance; Animals; Cell Count; Cell Differentiation; Cell Movement; Cell Survival; Cells, Cultured; Combined Modality Therapy; Electroencephalography; Erythropoietin; Fluorescent Antibody Technique; Hippocampus; Infusion Pumps, Implantable; Interneurons; Kainic Acid; Male; Neural Inhibition; Neuronal Plasticity; Neurons; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Seizures; Signal Processing, Computer-Assisted; Status Epilepticus; Stem Cell Transplantation

We explored the effects of exogenous and endogenous erythropoietin (EPO) in a seizure model of rat. Adult male Fischer 344 rats received continuous intraventricular infusion of EPO dissolved in saline containing 1mg/ml of rat serum albumin, anti-EPO antibody, saline containing 1mg/ml of rat serum albumin or combined EPO and neuropeptide Y (NPY) Y2-receptor antagonist. Animals were behaviorally evaluated for seizure development over 6h after kainic acid injection followed by immunohistochemical assays. Mortality rate, seizure severity, apoptotic cell death and abnormal cell proliferation in the hippocampus of EPO-treated epileptic rats were significantly attenuated, compared to control rats. Anti-EPO antibody in non-EPO-treated animals worsened seizures and CA1 neuronal cell death, while NPY Y2-receptor antagonist cancelled the therapeutic effects of exogenous EPO. Both exogenous and endogenous EPO might modulate seizure severity and protect the hippocampal neurons in epileptic rats, via novel mechanistic pathways involving blockade of epileptogenic cell formation coupled with NPY receptor modulation in the hippocampus.

Topics: Animals; Apoptosis; Autoantibodies; CA1 Region, Hippocampal; Cell Proliferation; Dentate Gyrus; Disease Models, Animal; Erythropoietin; Hematopoiesis; Kainic Acid; Male; Neurons; Neuropeptide Y; Rats; Rats, Inbred F344; Receptors, Neuropeptide Y; Seizures; Severity of Illness Index; Signal Transduction; Up-Regulation

To determine if posthypoxia treatment with erythropoietin (EPO) has protective effects against subsequent susceptibility to seizure related neuronal injury in rat pups subjected to acute hypoxia at P10.. Four groups of rats were manipulated at P10, as described below, then all received kainic acid (KA) (10 mg/kg i.p.) at P29: Hypoxia-NS-KA group (n = 11): subjected to acute hypoxia (down to 4% O2), and then immediately received saline i.p. Hypoxia-EPO-KA group (n = 10): subjected to acute hypoxia and then immediately received EPO (1,000 U/Kg i.p.). Normoxia-NS-KA group (n = 11): sham manipulated and injected with saline. Normoxia-EPO-KA group (n = 10): sham manipulated then immediately injected with EPO (1000 U/Kg i.p.). After receiving KA at P29, all rats were monitored using videotape techniques, and were sacrificed at P31. TUNEL and Hoechst stains to assess for apoptosis, and regular histology for hippocampal cell counts were performed.. Administration of the single dose of erythropoietin directly after an acute hypoxic event at P10 resulted at P29 in increased latency to forelimb clonus seizures, reduced duration of these seizures, protection against hippocampal cell loss, and decreased hippocampal apoptosis in the Hypoxia-EPO-KA group as compared to the Hypoxia-NS-KA group.. These data support the presence of favorable protective effects of erythropoietin against the long-term consequences of acute hypoxia in the developing brain and raise the possibility of its investigation as a potential neuroprotective agent after human neonatal hypoxic encephalopathy.

Topics: Animals; Animals, Newborn; Cell Count; Disease Models, Animal; Disease Susceptibility; Dose-Response Relationship, Drug; Erythropoietin; Excitatory Amino Acid Agonists; Hippocampus; Humans; Hypoxia; Hypoxia, Brain; Kainic Acid; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Seizures

Our objective was to establish a nonhuman primate model of perinatal asphyxia appropriate for preclinical evaluation of neuroprotective treatment strategies under conditions that closely resemble human neonatal emergencies, and to begin testing the safety and efficacy of erythropoietin neuroprotective treatment. Prior to delivery by hysterotomy, the umbilical cords of near term Macaca nemestrina (n = 8) were clamped for times ranging between 12 and 15 min. Animals received erythropoietin (5,000 U/kg/dose x 2 i.v., n = 3), or vehicle (n = 5) after resuscitation. We assessed physiologic parameters, continuous electroencephalogram, magnetic resonance imaging/spectroscopy, safety parameters and behavior. Animals were euthanized at 4 months of age. Mean birth weight was 507 +/- 62 g. Initial arterial pH ranged from 6.75 to 7.12, with base deficits of 17-25 mEq. Animals were flaccid at birth, with attenuated electroencephalograms, and seizures occurred in 3 of 8 animals. We demonstrated magnetic resonance imaging/spectroscopy changes consistent with hypoxia (elevated lactate levels were present in some animals), significant motor and behavioral abnormalities (particularly with 15 min of cord clamping), and evidence of gliosis at the time of death. We have established a reproducible model of moderate to severe perinatal hypoxic-ischemic injury in M. nemestrina newborns. This model, which combines structural, biochemical, and behavioral assessments over time can be used to assess the safety and efficacy of neuroprotective strategies.

Topics: Animals; Animals, Newborn; Asphyxia; Brain; Disease Models, Animal; Electroencephalography; Erythropoietin; Female; Fetal Monitoring; Gliosis; Hypoxia-Ischemia, Brain; Lactic Acid; Macaca nemestrina; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Neuroprotective Agents; Placental Circulation; Pregnancy; Seizures; Umbilical Cord

Recombinant human erythropoietin (r-Hu EPO) has been shown to exert neuroprotection in ischemic, excitotoxicity, trauma, convulsions and neurodegenerative disorders. Blood-brain barrier (BBB) leakage plays a role in the pathogenesis of many pathological states of the brain including neurodegenerative disorders. This study aimed to investigate the effects of r-Hu EPO on BBB integrity in pentylentetrazol (PTZ) induced seizures in rats. Seizures were observed and evaluated regard to latency and intensity for an hour. Macroscopical and spectrophotometrical measurement of Evans Blue (EB) leakage were observed for BBB integrity. r-Hu EPO was given intraperitoneally 24 h prior to seizure induction. Total seizure duration of 720+/-50 s after single PTZ administration (80 mg/kg i.p.) was declined to 190+/-40 s in r-Hu EPO pretreatment. A typical BBB breakdown pattern (i.e. staining in cerebellum, cerebral cortex, midbrain, hippocampus, thalamus and corpus striatum) was observed in rat brains with PTZ induced seizures; whereas, EPO pretreatment confined BBB leakage to cerebellum and cortical areas, and lessened the intensity of tonic-clonic seizures observed in PTZ seizures. The protective effect of r-Hu EPO on BBB permeability in seizures is a new and original finding. The protective action of r-Hu EPO in seizures and some of CNS pathologies warrant further investigations.

Topics: Animals; Blood-Brain Barrier; Capillary Permeability; Convulsants; Disease Models, Animal; Drug Antagonism; Erythropoietin; Hematinics; Injections, Intraperitoneal; Male; Pentylenetetrazole; Rats; Rats, Wistar; Reaction Time; Recombinant Proteins; Seizures

Anemia is common in patients with chronic kidney disease (CKD) and those who have received a kidney allograft. Anemia is most prevalent in kidney transplant recipients before and immediately after transplantation, but also can occur months after transplantation if the donor kidney begins to fail. Replacement therapy for CKD-related and posttransplantation anemia is effective through the administration of exogenous erythropoiesis-stimulating proteins. Darbepoetin alfa (Aranesp; Amgen Inc, Thousand Oaks, CA) is a unique erythropoiesis-stimulating protein that can be administered at an extended dosing interval relative to recombinant human erythropoietin because of its approximately 3-fold longer serum half-life. Although darbepoetin alfa has been shown to be an effective treatment for patients with anemia of CKD and anemia after kidney transplantation, limited data have been published showing efficacy in treating women with anemia of these conditions during pregnancy. We report a case of successful darbepoetin alfa treatment for severe anemia in a pregnant transplant recipient.

Topics: Adult; Anemia; Cesarean Section; Contraindications; Cyclosporine; Darbepoetin alfa; Erythropoietin; Female; Ferrous Compounds; Humans; Hydronephrosis; Immunosuppressive Agents; Kidney Transplantation; Nephrostomy, Percutaneous; Postoperative Complications; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy, High-Risk; Puerperal Disorders; Seizures; Sirolimus; Stents; Treatment Refusal

Erythropoietin (EPO), recognized for its central role in erythropoiesis, also mediates neuroprotection when the recombinant form (r-Hu-EPO) is directly injected into ischemic rodent brain. We observed abundant expression of the EPO receptor at brain capillaries, which could provide a route for circulating EPO to enter the brain. In confirmation of this hypothesis, systemic administration of r-Hu-EPO before or up to 6 h after focal brain ischemia reduced injury by approximately 50-75%. R-Hu-EPO also ameliorates the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis, and the toxicity of kainate. Given r-Hu-EPO's excellent safety profile, clinical trials evaluating systemically administered r-Hu-EPO as a general neuroprotective treatment are warranted.

Topics: Animals; Biotin; Blood-Brain Barrier; Brain Injuries; Erythropoietin; Female; Kainic Acid; Male; Mice; Mice, Inbred BALB C; Neuroprotective Agents; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Receptors, Erythropoietin; Recombinant Proteins; Seizures

To test efficacy and safety of recombinant human erythropoietin (r-HuEPO) administration in dogs and cats with naturally developing chronic renal failure.. Case series.. 6 client-owned dogs and 11 client-owned cats with chronic renal failure.. r-HuEPO was administered intravenously or subcutaneously. Erythropoietic effects were monitored by determining CBC, performing cytologic examination of bone marrow aspirates, and measuring serum iron concentration before and during treatment. Development of adverse effects was monitored by performing sequential clinical assessments, CBC, and serum biochemical tests and by measuring indirect blood pressure and anti-r-HuEPO antibody titers.. Administration of r-HuEPO increased RBC and reticulocyte counts, hemoglobin concentration, and Hct comparably in dogs and cats. Assessments of clinical well-being, including appetite, energy, weight gain, alertness, strength, and playfulness, were improved variably. Adverse effects, including anemia, anti-r-HuEPO antibody production, seizures, systemic hypertension, and iron deficiency, were demonstrated inconsistently in dogs and cats.. Anemia contributes to clinical manifestations of chronic renal failure in dogs and cats. Administration of r-HuEPO has the potential to resolve anemia and improve clinical well-being. However, its administration poses risks of antibody production and adverse effects associated with correction of RBC mass. Use of r-HuEPO in dogs and cats requires conscientious assessment of risks and benefits until homologous forms of erythropoietin are available.

Topics: Anemia; Animals; Blood Cell Count; Blood Chemical Analysis; Blood Pressure; Bone Marrow; Cat Diseases; Cats; Dog Diseases; Dogs; Erythrocyte Indices; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Seizures

An 18-year-old renal transplant patient presented with sudden onset of seizures almost 2 years after she received the graft. Diagnostic work-up was unrevealing except for magnetic resonance imaging abnormalities of the brain that resolved spontaneously 4 weeks later. In this brief report, we discuss the etiology of the seizures and neurological abnormalities in renal transplant patients in light of the findings of our patient.

Topics: Adolescent; Brain Diseases; Diagnosis, Differential; Erythropoietin; Female; Humans; Hypertension, Renal; Kidney Function Tests; Kidney Transplantation; Magnetic Resonance Imaging; Recombinant Proteins; Seizures

Topics: Aged; Blood Pressure; Erythropoietin; Female; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Renal Dialysis; Seizures

The purpose of this study was to estimate the net cost effect to Medicare of the increasing use of recombinant human erythropoietin (EPO) instead of red blood cell transfusions or androgens in the management of anemia for the approximately 100,000 hemodialysis patients in the U.S. End-Stage Renal Disease (ESRD) program. A computerized decision model that takes into account the effectiveness and possible side effects of transfusions, androgens, and EPO and predicts 1- and 5-yr direct medical costs to Medicare associated with each therapy was constructed. Probability estimates for clinical events were derived from the literature. Costs were assigned by use of the amounts Medicare pays providers of ESRD care for: (1) use of EPO, transfusions, and androgens; and (2) health care services related to the treatment of anemia (including complications of treatment and possible reductions in morbidity). For every 10,000 hemodialysis patients treated with EPO, net Medicare expenditures will be much greater than if only transfusions are used by $42,530,000 at 1 yr (6% of ESRD program costs) and by $118,050,000 at 5 yr and also much greater than if androgens are used (by $42,700,000 at 1 yr and $118,370,000 at 5 yr). The increase in cost was highly sensitive to the dose of EPO; moderately sensitive to changes in estimated anemia response rates for EPO, frequency of EPO-induced vascular access clotting, and reduction in cardiovascular or overall morbidity; and slightly sensitive to transfusion rates, estimated anemia response rates for androgens, frequency of EPO-induced seizure or hypertensive complications (stroke, myocardial infarction), frequency of transfusion-related viral infection, and frequency of androgen-induced virilization. Considering both effectiveness and side effects of alternative treatments for the anemia of ESRD, it was projected that the increasing use of EPO will markedly increase the cost to Medicare of ESRD medical care.

Topics: Androgens; Anemia; Blood Component Transfusion; Cost Control; Costs and Cost Analysis; Decision Support Techniques; Erythropoietin; Humans; Immunologic Factors; Iron Deficiencies; Kidney Failure, Chronic; Medicare; Recombinant Proteins; Renal Dialysis; Seizures; United States

Therapy with recombinant human erythropoietin (rHuEPO) can reverse anemia and improve the quality of life in anemic hemodialysis patients. However, therapy is costly and must be used efficiently. An initial rHuEPO dose less than 50 U/kg intravenously three times weekly may be adequate to achieve a hematocrit of 30-33% in many patients. Acquired iron deficiency is a common problem during rHuEPO therapy and must be prevented with oral and parenteral iron replacement to maintain the efficacy of rHuEPO. Patients should be monitored carefully for additional problems including: an increase in blood pressure; onset of seizures or headaches; increased blood potassium, phosphate, and creatinine concentrations; enhanced coagulability resulting in dialyzer and vascular access clotting; and myalgias with a 'flu-like' syndrome.

Topics: Anemia; Blood Pressure; Erythropoietin; Headache; Hematocrit; Humans; Iron Deficiencies; Kidney Failure, Chronic; Recombinant Proteins; Seizures

Topics: Adult; Blood Pressure; Erythropoietin; Glomerulonephritis; Humans; Male; Middle Aged; Nephrectomy; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Renal Dialysis; Seizures; Transfusion Reaction

Administration of recombinant erythropoietin (r-HuEPO) is an effective treatment for the anaemia of chronic renal failure, but in some patients it has been accompanied by elevated blood pressure. This study focuses on seven patients with end-stage renal failure, managed on haemodialysis, who developed probable hypertensive encephalopathy with seizures during treatment with r-HuEPO. All made a full recovery. The events were not clearly related to the haemoglobin concentrations achieved, and four patients have subsequently been restarted on r-HuEPO therapy at a reduced dose, resulting in a slower increase in haemoglobin with no recurrence of episodes of severe hypertension. Close attention needs to be paid to blood pressure in patients commencing erythropoietin therapy, and it seems prudent to aim for a gradual increase in haemoglobin concentration to allow the circulation to adapt to changes in oxygen delivery and haematocrit.

Topics: Adult; Aged; Blood Pressure; Erythropoietin; Female; Hemoglobins; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Seizures