Erythropoietin Research Papers - Academia.edu (original) (raw)

The present study was performed to investigate the effects of exhaustive long lasting exercise at moderate altitude on the time course of serum immunomodulatory peptides, vascular endothelial growth factor (VEGF) and serum erythropoietin... more

The present study was performed to investigate the effects of exhaustive long lasting exercise at moderate altitude on the time course of serum immunomodulatory peptides, vascular endothelial growth factor (VEGF) and serum erythropoietin (EPO). Thirteen well trained runners participated at the Swiss Alpine Marathon of Davos (distance 67 km, altitude difference 2300 m). Interleukin-6 was significantly elevated in the first 2h after the run. In contrast, tumor necrosis factor-a and both soluble tumor necrosis factor-a receptors I and II were increased after exercise termination and showed sustained serum concentrations the following days. N eopterin, a serum marker for the activation of the cellular immune system, was increased until day two after the run. Immediately after the run VEGF was significantly elevated and further increased 2.4-fold until day five post exercise (p = 0.005). EPO was also increased after exercise but reached its maximum 2 h after the run (2-fold increase; p = 0.004) and decreased thereafter. The main findings of our study are that prolonged strenuous exercise at moderate altitude induced a significant long lasting increase in serum VEGF and EPO which was accompanied by an activation of the immune system.

This dose-finding, placebo-controlled study evaluated the safety and efficacy of darbepoetin alfa administered every 3 weeks (Q3W) to anaemic patients receiving chemotherapy. In part A, patients (haemoglobin 4110 g/l) were randomised in a... more

This dose-finding, placebo-controlled study evaluated the safety and efficacy of darbepoetin alfa administered every 3 weeks (Q3W) to anaemic patients receiving chemotherapy. In part A, patients (haemoglobin 4110 g/l) were randomised in a 1:4 ratio to receive 1 of 6 doses of darbepoetin alfa (4.5, 6.75, 9.0, 12.0, 13.5 and 15.0 mg/kg) or placebo Q3W for 12 weeks. In part B, patients received open-label darbepoetin alfa. Patients (n=249) were evaluated for safety, haemoglobin endpoints and red blood cell (RBC) transfusions. Darbepoetin alfa given at doses ranging from 4.5 to 15.0 mg/kg Q3W was well tolerated and comparable to placebo in terms of safety. No neutralising antibodies were detected. All doses (from 4.5 to 15 mg/kg) reduced transfusions compared with placebo, and resulted in > 50% of patients achieving a haematopoietic response. Administration of darbepoetin alfa Q3W has a tolerable safety profile and effectively ameliorates anaemia due to chemotherapy. #

There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury. OBJECTIVE To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and... more

There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury. OBJECTIVE To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24-and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. INTERVENTIONS Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells. MAIN OUTCOMES AND MEASURES Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury. RESULTS There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% CI for the difference, −0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009). CONCLUSIONS AND RELEVANCE In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting.

The study investigated the influence of prolonged physical stress during survival training with food and fluid deprivation on the serum concentrations of erythropoietin (EPO). A group of 29 male subjects [mean age 22.2 (SD 2.8) years,... more

The study investigated the influence of prolonged physical stress during survival training with food and fluid deprivation on the serum concentrations of erythropoietin (EPO). A group of 29 male subjects [mean age 22.2 (SD 2.8) years, height 1.78 (SD 0.06) m, and body mass (rob) 73.5 (SD 8.6) kgl were studied for 5 days of multifactorial stress including restricted water intake (11 H20"day-1) and food intake (628 kJ' day-1) combined with physical exercise (estimated energy expenditure approximately 24 000 kJ" day-l) and sleep deprivation (20 h within 5 days). Blood samples were taken before (T1), after 72 h (T2) and 120h (T3) of physical stress, and after 48 h, (T4) and 72 h (T5) of recovery. The samples were analysed for EPO, and concentrations of serum iron (Fe), haptoglobin (Hapto), transferrin (Trans), ferritin (Fer), haemoglobin (Hb) and packed cell volume (PCV). The mb had decreased by 6.77kg at T3 (P<0.01) and 0.68 kg at T5. The EPO and Hapto decreased during the survival training (P <0.01) and increased during the recovery period (P < 0.01). The Fe increased during the survival training (P <0.01) and remained above the control concentrations during recovery (P <0.01). The Hapto decreased during the survival training (P < 0.01) and remained below control concentration at T4 and T5 (P <0.01). The Trans decreased continuously over the week (P <0.01). The Fer increased during the survival training (P <0.01) and

Background: Substances with performance enhancing properties appear on a continuum, ranging from prohibited performance enhancing drugs (PED) through dietary supplements to functional foods (FF). Anti-doping messages designed to dissuade... more

Background: Substances with performance enhancing properties appear on a continuum, ranging from prohibited performance enhancing drugs (PED) through dietary supplements to functional foods (FF). Anti-doping messages designed to dissuade athletes from using PEDs have been typically based on moralising sport competition and/or employing scare campaigns with focus on the negative consequences. Campaigns offering comparable and acceptable alternatives are nonexistent, nor are athletes helped in finding these for themselves. It is timely that social marketing strategies for anti-doping prevention and intervention incorporate media messages that complement the existing approaches by promoting comparable and acceptable alternatives to doping. To facilitate this process, the aim of this study was to ascertain whether a single exposure knowledge-based information intervention led to increased knowledge and subsequently result in changes in beliefs and automatic associations regarding performance enhancements. Methods: In a repeated measure design, 115 male recreational gym users were recruited and provided with a brief information pamphlet on nitrite/nitrate and erythropoietin as a comparison. Measures of knowledge, beliefs and automatic associations were taken before and after the intervention with at least 24 hours between the two assessments. The psychological tests included explicit measures of beliefs and cognitive attitudes toward FF and PED using a self-reported questionnaire and computerised assessments of automatic associations using the modified and shortened version of the Implicit Association Test. Results: The information based intervention significantly increased knowledge (p < 0.001), changed explicit beliefs in specific FF (p < 0.001) and shifted the automatic association of FF with health to performance (p < 0.001). Explicitly expressed beliefs and automatic associations appear to be independent. Conclusion: Evidence was found that even a single exposure to a persuasive positive message can lead to belief change and can create new or alter existing associations -but only in the specific domain. Interventions to change outcome expectations in a positive way could be a rewarding avenue for anti-doping. Effective social marketing campaigns for drug free sport should follow appropriate market segmentation and use targeted messages via promoting the natural form as opposed to the purified form of the main active ingredient.

The application of blood conservation strategies to minimise or avoid allogeneic blood transfusion is seen internationally as a desirable objective. Bloodless surgery is a relatively new practice that facilitates that goal. However, the... more

The application of blood conservation strategies to minimise or avoid allogeneic blood transfusion is seen internationally as a desirable objective. Bloodless surgery is a relatively new practice that facilitates that goal. However, the concept is either poorly understood or evokes negative connotations. Bloodless surgery is a term that has evolved in the medical literature to refer to a peri-operative team approach to avoid allogeneic transfusion and improve patient outcomes. Starting as an advocacy in the early 1960s, it has now grown into a serious practice being embraced by internationally respected clinicians and institutions. Central to its success is a coordinated multidisciplinary approach. It encompasses the peri-operative period with surgeons, anaesthetists, haematologists, intensivists, pathologists, transfusion specialists, pharmacists, technicians, and operating room and ward nurses utilising combinations of the numerous blood conservation techniques and transfusion alt...

The proper measures for assessing quality of life (QOL) in patients with chronic kidney disease (CKD) remain unclear. QOL measures are subjective or objective, functional or satisfaction-based, and generic or disease-specific. Treatment... more

The proper measures for assessing quality of life (QOL) in patients with chronic kidney disease (CKD) remain unclear. QOL measures are subjective or objective, functional or satisfaction-based, and generic or disease-specific. Treatment of end-stage renal disease with transplantation and treatment of anemia with erythropoietin in patients with CKD have been associated with dramatic improvements of QOL. Other factors such as age, ethnic or national background, stage of CKD, modality of dialytic therapy, exercise interventions, sleep disturbances, pain, erectile dysfunction, patient satisfaction with care, depressive affect, symptom burden, and perception of intrusiveness of illness may be associated with differential perception of QOL. Recent studies showed an association between assessment of QOL and morbidity and mortality in end-stage renal disease patients, suggesting the measures do matter. Further studies are necessary in patients with early stages of CKD and in children. QOL m...

supplementation in haemodialysis patients. No significant adverse reactions to iron therapy were observed. Background. The aim of this prospective study was to test a new protocol for iron supplementation in haemo-Key words:... more

supplementation in haemodialysis patients. No significant adverse reactions to iron therapy were observed. Background. The aim of this prospective study was to test a new protocol for iron supplementation in haemo-Key words: erythropoietin; ferritin; haemodialysis; iron; dialysis patients, as well as to assess the utility of intravenous different iron metabolism markers in common use and their 'target' values for the correction of iron deficiency. Methods. Thirty-three of 56 chronic haemodialysis patients were selected for long-term (6 months) i.v. Introduction iron therapy at 20 mg three times per week postdialysis based on the presence of at least one of the With the widespread utilization of rHuEpo in haemofollowing iron metabolism markers: percentage of dialysis, prolonged or chronic iron overload and transferrin saturation (%TSAT) <20%; percentage of haemosiderosis have almost disappeared. Eryhypochromic erythrocytes (%HypoE) >10% and thropoietin promotes the use of iron deposits in the serum ferritin (SF) <400 mg/l. Reasons for patient bone marrow, and consequently iron deficiency is a exclusion were active inflammatory or infectious disfrequent problem resulting in resistance to the full eases, haematological diseases, psychosis, probable effect of rHuEpo. It is well known that a negative iron iron overload (SF Á400 mg/l) and/or acute need of balance may occur-up to 2 g/year [1]-and it is not blood transfusion mostly due to haemorrhage and well established whether there is a compensatory change in renal replacement treatment. increase in intestinal absorption in haemodialysis Results. More than half (51.8%) of the patients of our patients when they are iron deficient [2-5]. Oral dialysis centre proved to have some degree of iron supplementation is plagued by poor patient adherence deficiency in spite of their regular oral iron due to frequent side-effects, and interference of other supplementation. At the start of the study the mean medication with the digestive absorption [6 ]. Several haemoglobin was 10.8 g/dl and increased after the 6 studies have demonstrated the utility of i.v. iron months of iron treatment to 12.8 g/dl (P<0.0001). supplementation in correcting anaemia and sparing The use of erythropoietin decreased from 118 rHuEpo [7-10]. However the multiple publications units/kg/week to 84 units/kg/week. The criterion for evaluating the criteria to detect and to treat patients iron supplementation with the best sensitivity/specifiwith iron deficiency and the several protocols adopted city relationship (100/87.9%) was ferritin <400 mg/l. to correct this situation clearly show that there is no Patients with ferritin <100 mg/l and those with ferritin consensus [11-18]. between 100 mg/l and 400 mg/l had the same increase We administered 20 mg iron i.v. post-dialysis on a in haemoglobin but other parameters of iron metabollong-term basis because it allows approximated conism were different between the two groups. tinuous availability of iron to be incorporated into Conclusions. Routine supplementation of iron in haemoglobin under the action of rHuEpo and allowed haemodialysis patients should be performed intraveneasy control to prevent the oversaturation of transferously. Target ferritin values should be considered indirin [19,20] and iron overload. vidually and the best mean haemoglobin values were We evaluated rHuEpo dose and haemoglobin during achieved at 6 months with a mean ferritin of 456 mg/l long-term i.v. iron therapy for 6 months and evaluated (variation from to 919 mg/l). The percentage of transthe best markers to monitor this therapy. Prior to this ferrin saturation, percentage of hypochromic erythrostudy, iron status was assessed on a 3-month basis by cytes and ferritin <100 mg/l, were not considered serum ferritin (SF) and the percentage of transferrin useful parameters to monitor routine iron saturation (%TSAT); iron supplementation was given orally as a routine and the i.v. route was reserved for

To evaluate the efficacy of once-monthly darbepoetin alfa in maintaining hemoglobin (Hb) levels between 10 and 12 g/dL in older subjects receiving darbepoetin alfa every 2 weeks. Design: A secondary analysis of a 29-week multicenter,... more

To evaluate the efficacy of once-monthly darbepoetin alfa in maintaining hemoglobin (Hb) levels between 10 and 12 g/dL in older subjects receiving darbepoetin alfa every 2 weeks. Design: A secondary analysis of a 29-week multicenter, open-label, single-arm study with an initial 2-week screening/baseline period, followed by a 20-week once-monthly darbepoetin alfa dose titration period and an 8-week evaluation period. Setting: Twenty treatment centers in the United States. Participants: Subjects with CKD who were not receiving dialysis and whose hemoglobin levels were Ն10 g/dL with darbepoetin alfa every 2 weeks. Intervention: Darbepoetin alfa administered once monthly and titrated to maintain Hb level between 10 and 12 g/dL, inclusive. Measurements: The proportion of subjects maintaining a mean Hb concentration of 10 to 12 g/dL, inclusive, while receiving once-monthly darbepoetin alfa during the evaluation period (weeks 21 to 29); the mean change in Hb levels and darbepoetin alfa doses between baseline and the evaluation period; and the treatment relationship, frequency, severity, and outcomes of all adverse events. Analyses were stratified by age (Ͻ65, Ն65, and Ն75 years). Results: Seventy-nine percent of subjects aged Ն65 years and 80% of subjects aged Ն75 years maintained their Hb levels within the specified target range, compared with 80% of subjects aged Ͻ65 years who maintained their Hb levels within the specified target range. Hemoglobin levels and darbepoetin alfa doses did not change significantly from baseline to the evaluation period. Darbepoetin alfa administered once monthly was well tolerated in all age groups. Conclusion: Darbepoetin alfa administered once monthly effectively maintained target Hb levels in older subjects with CKD (not receiving dialysis) who were maintained previously with an every 2 weeks darbepoetin alfa regimen.

In assessing erythropoietic agents for chemotherapy-induced anemia, traditional single time-point end points (e.g., hematopoietic response [HR]) fail to reflect clinical benefits over the entire therapy course. Area under the hemoglobin... more

In assessing erythropoietic agents for chemotherapy-induced anemia, traditional single time-point end points (e.g., hematopoietic response [HR]) fail to reflect clinical benefits over the entire therapy course. Area under the hemoglobin change curve (Hb AUC) is introduced as an alternative measure, and its reliability, clinical significance, and superiority are assessed.

Introduction: Erythropoiesis-stimulating agents (ESAs) prevent transfusions among anemic patients with chronic kidney disease (CKD). Clinical trials, meta-analyses, and guidelines identify arterial and venous thromboembolism as well as... more

Introduction: Erythropoiesis-stimulating agents (ESAs) prevent transfusions among anemic patients with chronic kidney disease (CKD). Clinical trials, meta-analyses, and guidelines identify arterial and venous thromboembolism as well as myocardial event risks with the traditional ESAs, erythropoietin (EPO), and darbepoietin. Side effects of anemia treatment, considering frequency and dosage of treatment as well as targeted hemoglobin levels when utilizing ESAs, greatly impact overall well-being and the quality of life. There is a need for less frequent but equally effective ESAs in this setting. Areas covered: The three generations of ESAs used in CKD-associated anemia are described. Cost effectiveness of the utilization of these therapies, in addition to emerging therapies, is also presented. The few clinical and controlled trials only highlight the need for clarity in molecular biology surrounding the components that control EPO levels and utilization. Expert opinion: Anemia associated with CKD is an important area for development of newer therapies which are potentially safer and more convenient to administer.

To verify the hypothesis of an early impairment of erythropoietin (Epo) production and to assess the adequacy of its circulating levels in diabetic nephropathy, we investigated Epo values in 18 microalbuminuric type 2 diabetic patients... more

To verify the hypothesis of an early impairment of erythropoietin (Epo) production and to assess the adequacy of its circulating levels in diabetic nephropathy, we investigated Epo values in 18 microalbuminuric type 2 diabetic patients with normal renal function (7 anaemic and 11 nonanaemic), 24 subjects with uncomplicated iron-deficiency anaemia, and 15 healthy controls comparable for sex and age. MeanFS.D. plasma Epo level was 56.4F12.7 mU/mL in iron-deficient patients and 9.3F2.6 mU/mL in controls. In diabetic groups, meanFS.D. Epo level was 11.38F3.65 mU/mL in nonanaemic and 49.12F6.44 mU/mL in anaemic subjects. No significant difference ( PN.05) in Epo values was found between controls and nonanaemic diabetic patients. Anaemic diabetics and iron-deficient subjects had significantly higher values than the nonanaemic groups ( PN.001). An inverse significant relation between Epo levels and Hb concentration resulted in both anaemic diabetics (r=À.44, PN.05) and iron-deficient patients (r=À.61, P=.001). Analysis of covariance ( PN.05) and comparison of the two regression lines (t=0.4, df=29, PN.05) did not show any significant difference between diabetic patients with anaemia and iron-deficient patients. These results suggest that normochromic anaemia observed in microalbuminuric diabetic patients with normal renal function is not due to Epo deficiency, and circulating levels of this hormone are suitably increased with regard to Hb concentration. D

Patients who suffer from chronic renal failure (CRF) tend to suffer from an associated anemia as well. Therefore, it is essential to know the hemoglobin (Hb) levels in these patients. The aim of this paper is to predict the hemoglobin... more

Patients who suffer from chronic renal failure (CRF) tend to suffer from an associated anemia as well. Therefore, it is essential to know the hemoglobin (Hb) levels in these patients. The aim of this paper is to predict the hemoglobin (Hb) value using a database of European hemodialysis patients provided by Fresenius Medical Care (FMC) for improving the treatment of this kind of patients. For the prediction of Hb, both analytical measurements and medication dosage of patients suffering from chronic renal failure (CRF) are used. Two kinds of models were trained, global and local models. In the case of local models, clustering techniques based on hierarchical approaches and the adaptive resonance theory (ART) were used as a first step, and then, a different predictor was used for each obtained cluster. Different global models have been applied to the dataset such as Linear Models, Artificial Neural Networks (ANNs), Support Vector Machines (SVM) and Regression Trees among others. Also a relevance analysis has been carried out for each predictor model, thus finding those features that are most relevant for the given prediction.

Erythropoietin (Epo) has neuroprotective and neurotrophic eVects and improves cognitive function in animal models of neurodegenerative and neuropsychiatric illness. In humans, weekly Epo administration over 3 months improves cognitive... more

Erythropoietin (Epo) has neuroprotective and neurotrophic eVects and improves cognitive function in animal models of neurodegenerative and neuropsychiatric illness. In humans, weekly Epo administration over 3 months improves cognitive function in schizophrenia. The neural underpinnings and time-course of this eVect of Epo are currently unknown. It is also unclear whether the cognitive improvement reXects direct neurobiological actions or is secondary to hematological eVects. We therefore assessed the actions of single administration of Epo (40,000 IU) vs. saline to healthy volunteers on cognitive and neural measures of executive function using a verbal Xuency task and N-back working memory (WM) paradigm during functional magnetic resonance imaging (fMRI) on day 3 and 7 after administration in two separate cohorts of subjects. Epo modulated neuronal response in a fronto-parietal network during WM performance at both time points; on day 3 after administration, activation was increased in lefthemisphere frontal and cingulate cortex and reduced in the right parietal cortex; in contrast, neural response was enhanced in a right-lateralized fronto-parietal network and reduced in left-side regions 1 week post-administration. In addition, Epo-treated volunteers displayed improved verbal Xuency performance 1 week post-administration. These eVects occurred in the absence of changes in hematological measures suggesting that they reXect direct neurobiological actions of Epo. The Wndings are co nsistent with enduring eVects of Epo on neurotrophic signaling and induction of neurochemical changes over time in neural networks typically aVected in neuropsychiatric illness. The present study supports the notion that Epo may have clinical applications in the treatment of psychiatric disorder characterized by cognitive dysfunction.

Background context: Ketorolac Tromethamine (ketorolac) is a nonsteroidal anti-inflammatory drug (NSAID) with proven efficacy in decreasing postoperative pain in various surgical settings, including the treatment of spine deformities.... more

Background context: Ketorolac Tromethamine (ketorolac) is a nonsteroidal anti-inflammatory drug (NSAID) with proven efficacy in decreasing postoperative pain in various surgical settings, including the treatment of spine deformities. However, some studies have raised questions regarding the potential side effects of this agent, such as increased bleeding and inhibition of bony fusion.Purpose: This study was conducted to determine whether there is

Background: Anemia is a common finding in heart failure (HF) patients and has been associated with increased morbidity and mortality. It is generally denominated as anemia of chronic disease (ACD), but the association with true ferropenic... more

Background: Anemia is a common finding in heart failure (HF) patients and has been associated with increased morbidity and mortality. It is generally denominated as anemia of chronic disease (ACD), but the association with true ferropenic anemia is common. Many studies have investigated the effects of treating anemia in HF patients with either erythropoietin alone or combination of erythropoietin and intravenous iron. However, the effect of iron supplementation alone in HF patients with ACD, ferropenic anemia, or both is unknown. Methods and Results: IRON-HF study is a multicenter, investigator initiated, randomized, double-blind, placebo controlled trial that will enroll anemic HF patients with relatively preserved renal function, low transferrin saturation, low iron levels, and low to moderately elevated ferritin levels. Interventions are iron sucrose intravenously 200 mg once per week for 5 weeks, ferrous sulfate 200 mg by mouth 3 times per day for 8 weeks, or placebo. The primary objective is to assess the impact of iron supplementation (intravenously or by mouth) compared with placebo in HF patients with anemia from deficient iron availability. The primary end point is variation of peak oxygen consumption assessed by ergospirometry over 3-month follow-up. Secondary end points include functional class, brain natriuretic peptide levels, quality of life scores, left ventricular ejection fraction, adverse events, HF hospitalization, and death. Conclusions: The results of IRON-HF should help to clarify the potential clinical impact of mild to moderate anemia correction in HF patients. (J Cardiac Fail 2007;13:14e17)

Improvement of long-term drug release and design of mechanically more stable encapsulation devices are still major challenges in the field of cell encapsulation. This may be in part due to the weak in vivo stability of calcium-alginate... more

Improvement of long-term drug release and design of mechanically more stable encapsulation devices are still major challenges in the field of cell encapsulation. This may be in part due to the weak in vivo stability of calcium-alginate beads and to the use of inactive biomaterials and inert scaffolds that do not mimic the physiological situation of the normal cell milieu. We hypothesized that designing biomimetic cell-hydrogel capsules might promote the in vivo long-term functionality of the enclosed drug-secreting cells and improve the mechanical stability of the capsules. Biomimetic capsules were fabricated by coupling the adhesion peptide arginine glycine aspartic acid (RGD) to alginate polymer chains and by using an alginate-mixture providing a bimodal molecular weight distribution. The biomimetic capsules provide cell adhesion for the enclosed cells, potentially also leading to mechanical stabilization of the cell-polymer system. Strikingly, the novel cell-hydrogel system significantly prolonged the in vivo long-term functionality and drug release, providing a sustained erythropoietin delivery during 300 days without immunosuppressive protocols. Additionally, controlling the cell-dose within the biomimetic capsules enables a controlled in vitro and in vivo drug delivery. Biomimetic cell-hydrogel capsules provide a unique microenvironment for the in vivo long-term de novo delivery of drugs from immobilized cells.

Darbepoetin alfa, an erythropoiesis-stimulating protein, has a longer serum half-life than recombinant human erythropoietin, allowing less-frequent administration. This study aimed to demonstrate that once-monthly (QM) darbepoetin alfa... more

Darbepoetin alfa, an erythropoiesis-stimulating protein, has a longer serum half-life than recombinant human erythropoietin, allowing less-frequent administration. This study aimed to demonstrate that once-monthly (QM) darbepoetin alfa administration would maintain haemoglobin (Hb) concentrations in subjects with chronic kidney disease (CKD) not receiving dialysis who had previously been administered darbepoetin alfa every 2 weeks (Q2W). Methods: This was a multicentre study in which subjects with CKD receiving stable Q2W darbepoetin alfa doses and with stable Hb (100-130 g/L) were started on QM darbepoetin alfa dosing. The initial QM darbepoetin alfa dose was equivalent to the cumulative darbepoetin alfa dose administered during the month preceding enrolment. Darbepoetin alfa doses were titrated to maintain Hb concentrations between 100 and 130 g/L. The primary endpoint was the proportion of subjects maintaining mean Hb 3 100 g/L during the evaluation period (weeks 21-33). Results: Sixty-six subjects were enrolled in the study and all received at least one dose of darbepoetin alfa; 55 (83%) had mean Hb 3 100 g/L during evaluation. Mean (SD) Hb concentrations at baseline and during the evaluation period were 119 (8.7) g/L and 114 (9.8) g/L, respectively. The median QM darbepoetin alfa dose at baseline and during the evaluation period was 80 mg. Darbepoetin alfa was considered to be well-tolerated. Conclusion: Patients with CKD not receiving dialysis who are receiving darbepoetin alfa Q2W can be safely and effectively extended to darbepoetin alfa QM. Dosing QM may simplify anaemia management for patients and health-care providers.

People living with end-stage kidney disease (ESKD) often develop anaemia. Erythropoiesis-simulating agents (ESAs) are often given to people living with ESKD to maintain haemoglobin at a level to minimise need for transfusion. However,... more

People living with end-stage kidney disease (ESKD) often develop anaemia. Erythropoiesis-simulating agents (ESAs) are often given to people living with ESKD to maintain haemoglobin at a level to minimise need for transfusion. However, about 5% to 10% of patients with ESKD exhibit resistance to ESAs, and observational studies have shown that patients requiring high doses of ESA are at increased risk of mortality. This review aimed to study the effects of interventions for the treatment of ESA-resistant anaemia in people with ESKD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE for randomised controlled trials (RCT) that involved participants with ESKD on dialysis or who were pre-dialysis patients with chronic kidney disease (stage 5). Date of last search: April 2013. ESA resistance was defined as failure to achieve or maintain haemoglobin/haematocrit levels within the desired target range despite appropriate ESA doses (erythropoietin ≥ 45...

The glycoprotein hormone erythropoietin is an essential viability and growth factor for the erythrocytic progenitors in the bone marrow. Tissue hypoxia is the main stimulus for the synthesis of the hormone in the kidneys and the liver.... more

The glycoprotein hormone erythropoietin is an essential viability and growth factor for the erythrocytic progenitors in the bone marrow. Tissue hypoxia is the main stimulus for the synthesis of the hormone in the kidneys and the liver. Endogenous erythropoietin and recombinant human erythropoietin (rHu-EPO) are similar with respect to their biological and chemical properties except for some microheterogeneities in their 4 carbohydrate chains. Generic products and alternatives to rHu-EPO are in development. Renal anemia can be corrected by rHu-EPO in a dose-dependent and predictable way without major side effects apart from a possible increase in arterial blood pressure. The optimal target hematocrit still needs to be defined. There are rare reports of antibody formation towards rHu-EPO in humans. Patients suffering from non-renal anemias may also benefit from the prescription of rHu-EPO. The drug has been approved for treatment of tumor patients with platinum-induced anemia. The cost-effectiveness and medical justification of the administration of rHu-EPO in tumor patients with respect to its positive effects on tumor oxygenation, tumor growth inhibition and support of chemo-and radiotherapy is still a matter of debate. In surgical patients, the pharmacological application of rHu-EPO can increase the yield of blood units in autologous blood donation programs and lower the severity and duration of postoperative anemia, if applicated some days prior to surgery. While rHu-EPO is a godsend in medical practice, its abuse as an performance enhancing drug by athletes in endurance sports is an unethical and potentially dangerous procedure. Unequivocal methods for detection of rHu-EPO doping still need to be established. studies of the pathophysiology and pharmacology of EPO . In all likelihood, rHu-EPO is today the best selling drug in the world (estimated sales 5,000 millions US $ per year).

The liver plays an important role in the production of haemopoietic hormones. It acts as the primary site of synthesis of erythropoietin (EPO) in the fetal stage, and it is the predominant thrombopoietin (TPO)-producing organ for life. In... more

The liver plays an important role in the production of haemopoietic hormones. It acts as the primary site of synthesis of erythropoietin (EPO) in the fetal stage, and it is the predominant thrombopoietin (TPO)-producing organ for life. In contrast to that of EPO and other liver proteins, the hepatic synthesis of TPO is influenced little by external signals. Hepatocytes express the TPO gene in a constitutive way, i.e. irrespective of the level of platelets in blood. Megakaryocytes and platelets remove the hormone from blood by means of their high-affinity TPO receptors. Normally, the plasma level of TPO is relatively low ( approximately 10(-12) mol/l). However, in thrombocytopenic states due to marrow failure or bleeding, the concentration of circulating TPO may increase greatly. The simple feedback regulation by TPO and its target cells is efficient in maintaining constant platelet numbers in healthy people. Persisting thrombocytopenia develops only in severe liver or marrow failure...

Since the very early manned missions in space, a state of anemia associated with reduced erythropoietin levels and reduced plasma volume was disclosed. The reduction in red blood cell mass is driven by a process of selective hemolysis,... more

Since the very early manned missions in space, a state of anemia associated with reduced erythropoietin levels and reduced plasma volume was disclosed. The reduction in red blood cell mass is driven by a process of selective hemolysis, which has been named neocytolysis. This phenomenon also occurs in people living at a high altitude who descend rapidly to sea level. The origin of the signal leading to destruction of newly produced red blood cells probably is located in central circulation, but the operating mechanism is unknown. The importance of plasma cell volume reduction in the genesis of a lower red cell mass also is supported by the inverse correlation seen at moderate altitude. People arriving at moderate altitude have increased erythropoietin concentration that decreases after a few days and is in inverse correlation with central venous pressure. Studies under simulated microgravity conditions in human beings (bed rest, head-down tilt at ؊6°, water immersion) and in rats provide further insight in unraveling the mechanism of astronauts' anemia, a problem difficult to study in space because of the limited availability of spaceflights. Semin Nephrol 25:379-387

Preterm infants are at risk for neurodevelopmental sequelae even in absence of major cerebral lesions. The hypothesis that Human Recombinant Erythropoietin (rEpo) could improve the neurodevelopmental outcome in risk neonates has raised... more

Preterm infants are at risk for neurodevelopmental sequelae even in absence of major cerebral lesions. The hypothesis that Human Recombinant Erythropoietin (rEpo) could improve the neurodevelopmental outcome in risk neonates has raised the highest interest in recent years. A group of preterm neonates born at a gestational age ≤ 30 weeks and free from major cerebral lesions or major visual impairment, were included in the study if they had a complete neurologic evaluation for at least 24 months of postmenstrual age. They were assigned to group I in the case they had been treated with rEpo or group II if untreated. The aim was to evaluate whether rEpo, given at the high cumulative doses utilized for hematologic purposes, is able to improve the neurodevelopmental outcome in preterm infants born at a gestational age ≤ 30 weeks. A group of 104 preterm neonates were studied: 59 neonates who received rEpo for 6.9 ± 2.4 weeks at a median cumulative dose of 6300 UI/Kg (6337 ± 2434 UI/Kg), st...

Preterm infants, especially those with extremely low birth weight (ELBW) are exposed to frequent blood draws as part of their care in the neonatal intensive care unit. ELBW infants develop the anemia of prematurity (AOP), a... more

Preterm infants, especially those with extremely low birth weight (ELBW) are exposed to frequent blood draws as part of their care in the neonatal intensive care unit. ELBW infants develop the anemia of prematurity (AOP), a hypo-proliferative anemia marked by inadequate production of erythropoietin (Epo). Treatment of AOP includes red blood cell transfusions, which are given to preterm infants based on indications and guidelines (hematocrit/hemoglobin levels, ventilation and oxygen need, apneas and bradycardias, poor weight gain) that are relatively non-specific. In this article we review recent studies evaluating transfusion guidelines, discuss ways to decrease phlebotomy losses and examine the use of red cell growth factors such as Epo in preventing and treating anemia in preterm infants. Semin Perinatol 33:29-34 Published by Elsevier Inc.

4 weeks time in low dose group, blood analysis including: oxidant (malondialdehyde [MDA]) concentration, and anti-oxidant (total antioxidant [TA]) parameters were analyzed. Finally, the differences among three groups were analyzed by SPSS... more

4 weeks time in low dose group, blood analysis including: oxidant (malondialdehyde [MDA]) concentration, and anti-oxidant (total antioxidant [TA]) parameters were analyzed. Finally, the differences among three groups were analyzed by SPSS 16.0 Software.

Background: Hemoglobin levels measured after hemodialysis, as compared to hemoglobin levels measured before hemodialysis, are suggested to be a more accurate reflection of the hemoglobin levels between hemodialysis sessions, and to be a... more

Background: Hemoglobin levels measured after hemodialysis, as compared to hemoglobin levels measured before hemodialysis, are suggested to be a more accurate reflection of the hemoglobin levels between hemodialysis sessions, and to be a better reference point for adjusting erythropoietin dosing.
Objectives: The aim of this study was to compare the hemoglobin levels before and after hemodialysis, to calculate the required erythropoietin doses based on these levels, and to develop a model to predict effective erythropoietin dosing.
Patients and Methods: In this cross-sectional study, the hemoglobin levels of 52 patients with end-stage renal disease were measured before and after hemodialysis. The required erythropoietin doses and the differences in cost were calculated based on the hemoglobin levels before and after hemodialysis. A model to predict the adjusted erythropoietin dosages based on post-hemodialysis hemoglobin levels was proposed.
Results: Hemoglobin levels measured after hemodialysis were significantly higher than the hemoglobin levels before hemodialysis
(11.1  1.1 vs. 11.9  1.2 g/dL, P < 0.001, 7% increase). The mean required erythropoietin dose based on post-hemodialysis
hemoglobin levels was significantly lower than the corresponding erythropoietin dose based on pre-hemodialysis hemoglobin levels
(10947  6820 vs. 12047  7542 U/week, P < 0.001, 9% decrease). The cost of erythropoietin was also significantly lower when
post-hemodialysis levels were used (15.96  9.85 vs. 17.57  11.00 dollars/patient/week, P < 0.001). This translated into 83.72 dollars/
patient/year in cost reduction. The developed model for predicting the required dosage is: Erythropoietin (U/week) = 43540.8 +
(-2734.8)Post-hemodialysis Hb* (g/dL). [(R2) = 0.221; *P < 0.001].
Conclusions: Using post-hemodialysis hemoglobin levels as a reference point for erythropoietin dosing can result in significant
dose and cost reduction, and can protect hemodialysis patients from hemoconcentration. The prediction of the erythropoietin
adjusted dosage based on post-hemodialysis Hb may also help in avoiding overdosage.

Despite its high prevalence, anemia often does not receive proper clinical attention, and detection, evaluation, and management of iron deficiency anemia and iron-restricted erythropoiesis can possibly be an unmet medical need. A... more

Despite its high prevalence, anemia often does not receive proper clinical attention, and detection, evaluation, and management of iron deficiency anemia and iron-restricted erythropoiesis can possibly be an unmet medical need. A multidisciplinary panel of clinicians with expertise in anemia management convened and reviewed recent published data on prevalence, etiology, and health implications of anemia as well as current therapeutic options and available guidelines on management of anemia across various patient populations and made recommendations on the detection, diagnostic approach, and management of anemia. The available evidence confirms that the prevalence of anemia is high across all populations, especially in hospitalized patients. Anemia is associated with worse clinical outcomes including longer length of hospital stay, diminished quality of life, and increased risk of morbidity and mortality, and it is a modifiable risk factor of allogeneic blood transfusion with its own inherent risks. Iron deficiency is usually present in anemic patients. An algorithm for detection and management of anemia was discussed, which incorporated iron study (with primary emphasis on transferrin saturation), serum creatinine and glomerular filtration rate, and vitamin B 12 and folic acid measurements. Management strategies included iron therapy (oral or intravenous), erythropoiesis-stimulating agents, and referral as needed.

La anemia es muy frecuente en los pacientes médicos y quirúrgicos ingresados en la Unidad de Cuidados Intensivos (UCI), siendo generalmente de origen multifactorial. Para evitar los efectos deletéreos de la anemia, un 40% de estos... more

La anemia es muy frecuente en los pacientes médicos y quirúrgicos ingresados en la Unidad de Cuidados Intensivos (UCI), siendo generalmente de origen multifactorial. Para evitar los efectos deletéreos de la anemia, un 40% de estos pacientes suele ser transfundido, elevándose esta cifra al 70% si la estancia en UCI supera los 7 días. Sin embargo, la transfusión de sangre alogénica se asocia con un aumento dosis-dependiente de la morbilidad y mortalidad. Por el contrario, la administración de eritropoyetina recombinante junto con suplementos de hierro, especialmente hierro endovenoso, estimula la eritropoyesis y disminuye la necesidad de transfusión, aunque no desciende la mortalidad. Es necesario por tanto realizar más estudios, con poder estadístico suficiente y período de seguimiento adecuado, para conocer si el tratamiento de la anemia del paciente crítico con eritropoyetina y con hierro endovenoso mejora el pronóstico de estos pacientes, así como para optimizar las pautas y dosis de dichos tratamientos.

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In the present study an attempt has been made to analysis of the chronic kidney disease (CKD) which is a global public health problem. Understanding the relationship between CKD and other chronic diseases is important to developing a... more

In the present study an attempt has been made to analysis of the chronic kidney disease (CKD) which is a global public health problem. Understanding the relationship between CKD and other chronic diseases is important to developing a public health policy to improve outcomes. This report contains, how the food habit could be changed with the change of cultural habituation. However, despite the magnitude of the resources committed to the treatment to show about the kidney function, causes of kidney disease and conceptual framework on different type of renal calculi and its prevention and some giving recommendation. It is now well recognized that the prevalence of CKD is increasing all over the world. The global annual growth of number of ESRD patients is reported at 7%. In view of high disease burden, it became an uneven distribution, expensive treatment and because of fact that organized preventive strategies which are not in place in most countries. So, CKD has assumed the proportions of a significant public health problem.