losartan-potassium and Weight-Loss

CKD is a major public health problem in the developed and the developing world. The degree of proteinuria associated with renal failure is a generally well accepted marker of disease severity. Agents with direct antiproteinuric effects are highly desirable therapeutic strategies for slowing, or even halting, progressive loss of kidney function. We review progress on therapies acting further downstream of the renin-angiotensin-aldosterone system pathway (e.g., transforming growth factor-beta antagonism, endothelin antagonism) and on those acting independent of the renin-angiotensin-aldosterone system pathway. In all, we discuss 26 therapeutic targets or compounds and 2 lifestyle changes (dietary modification and weight loss) that have been used clinically for diabetic or nondiabetic kidney disease. These therapies include endogenous molecules (estrogens, isotretinoin), biologic antagonists (monoclonal antibodies, soluble receptors), and small molecules. Where mechanistic data are available, these therapies have been shown to exert favorable effects on glomerular cell phenotype. In some cases, recent work has indicated surprising new molecular pathways for some therapies, such as direct effects on the podocyte by glucocorticoids, rituximab, and erythropoietin. It is hoped that recent advances in the basic science of kidney injury will prompt development of more effective pharmaceutical and biologic therapies for proteinuria.

Topics: Animals; Antibodies, Monoclonal, Murine-Derived; Antihypertensive Agents; Calcineurin Inhibitors; Endothelins; Erythropoietin; Fatty Acids, Omega-3; Feeding Behavior; Glucocorticoids; Humans; Kidney Diseases; Mice; Proteinuria; Rats; Renin-Angiotensin System; Rituximab; Transforming Growth Factors; Weight Loss

This prospective, randomised pilot study was designed to evaluate safety, feasibility and efficacy of recombinant human erythropoietin (rhEPO) in the prevention and treatment of chemotherapy-induced anaemia in children with solid tumours. 20 children (age 4-18 years) undergoing cyclic combination chemotherapy were randomised either to a control group or to receive rhEPO at a dose of 150 U/kg/dose subcutaneously three times/week for a minimum of 12 weeks or three chemotherapy cycles. Of 15 evaluable patients, 8 were randomised to the rhEPO group and 7 to the control group. RhEPO-treated patients showed an increase in the haematocrit over the first 8 weeks of therapy, with a significantly higher mean haematocrit at week 8 (33.2 +/- 2.1% versus 39.3 +/- 4.2% in the control and rhEPO groups, respectively, P < 0.05). Similarly, significantly higher haemoglobin concentrations could be demonstrated in the rhEPO group by week 8 (11.06 +/- 1.35 g/dl versus 13.11 +/- 1.13 g/dl in the control and rhEPO groups, respectively, P < 0.05), with higher precycle haemoglobin before chemotherapy cycles 3 and 4 and higher midcycle haemoglobin between cycles 3 and 4. There was a trend towards a reduction of transfusion requirements during the 3rd month of therapy in rhEPO patients. The results of this pilot study indicate a significant benefit of rhEPO in children treated with intensive combination chemotherapy regimens. Further studies should target issues such as appropriate dosing, timing and duration of rhEPO therapy in children with cancer.

Topics: Adolescent; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Child; Child, Preschool; Erythropoietin; Ferritins; Hemoglobins; Humans; Iron; Pilot Projects; Prospective Studies; Recombinant Proteins; Weight Loss

This study was aimed at evaluating whether anemia could be prevented in unselected weight-losing cancer patients on anti-inflammatory treatment by early and prophylactic treatment with recombinant human erythropoietin (rhEPO) and whether such a benefit could be translated into improved physical function and metabolic efficiency. One hundred eight cancer patients who experienced progressive cachexia due to solid, mainly gastrointestinal tumors were randomized to receive twice daily a cyclo-oxygenase inhibitor (controls; indomethacin, 50 mg twice a day) or indomethacin and erythropoietin, provided on individual basis to prevent development of progressive anemia (study patients; indomethacin, 50 mg twice a day plus rhEPO; range, 12,000-30,000 units per week). All patients were treated and followed up until death or to preterminal stage. Biochemical tests (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurements of respiratory gas exchanges before and during exercise were performed before institution of treatments and then at regular intervals during the treatment period (2-30 months after start). Study and control patients did not differ in survival. rhEPO prevented development of anemia during the entire observation period. This was associated with a significantly more preserved maximum exercise capacity in study patients compared to control patients during the follow-up period (101 +/- 10 versus 66 +/- 6 W; P < 0.0001), based on more effective ventilation and whole-body respiratory gas exchanges. These improvements were also evident when exercise performance was normalized to lean body mass, an indirect measure of the skeletal muscle mass. The metabolic efficiency, expressed as oxygen uptake per watt produced, was also significantly preserved in rhEPO-treated patients compared to controls (14.1 +/- 1.1 versus 16.3 +/- 0.9 ml O2/W, P < 0.05). Our results demonstrate that institution of early and prophylactic rhEPO treatment to patients with progressive cancer prevents development of tumor-induced anemia. This achievement was associated with a better preserved exercise capacity, which is explained in part by improved whole-body metabolic and energy efficiency during work load.

Topics: Aged; Anemia; Anti-Inflammatory Agents, Non-Steroidal; Cachexia; Cyclooxygenase Inhibitors; Energy Metabolism; Erythropoietin; Exercise Test; Female; Humans; Indomethacin; Male; Middle Aged; Neoplasms; Prospective Studies; Pulse; Recombinant Proteins; Weight Loss

Patients with haematological malignancies undergoing allogeneic BMT were randomised to treatment with recombinant human erythropoietin (rHuEPO) (n = 25) or placebo (n = 25). rHuEPO was given at 200 U/kg daily for 4 weeks and 200 U/kg twice weekly for a further 4 weeks. The groups were similar regarding several prognostic factors. There were no differences between the two groups regarding time to engraftment, fever, hospitalisation, GVHD, infections, haemorrhages, transplant-related mortality, relapse and survival. However, more patients in the control group had a raised serum creatinine (43% vs 14%; p = 0.04). Red blood cell (RBC) transfusion requirements for the first 2 months after BMT were significantly lower in the rHuEPO group compared with the control group (5 units vs 10; p = 0.04). Time to unsupported Hb > 70 g/l was less in patients treated with rHuEPO (14 days vs 24; p = 0.03). No effect was seen on platelet engraftment or the number of transfused platelet units. Two patients in the control group compared with none in the rHuEPO group became refractory to platelet transfusions. According to the protocol the study drug was reduced (Hb > 100) or discontinued (Hb > 120) for a mean of 3.6 weeks among 11 rHuEPO patients compared with 1.9 weeks among 7 controls (p = 0.02). Seven of the treated patients compared with none of the controls reached Hb > 120 during the study period (p = 0.004). Among the rHuEPO treated patients, EPO-levels were significantly higher than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Blood Cell Count; Blood Transfusion; Bone Marrow Transplantation; Child; Double-Blind Method; Erythropoiesis; Erythropoietin; Female; Hematologic Diseases; Hemoglobins; Humans; Immunologic Factors; Incidence; Leukemia; Male; Middle Aged; Recombinant Proteins; Reticulocytes; Survival Analysis; Weight Loss

Erythropoietin (EPO) is the cytokine that regulates red blood cell production. Less understood is the nonerythroid action of EPO, including metabolic regulation of fat accumulation and glucose homeostasis. Although EPO treatment increased hematocrit and improved glucose tolerance in male and female mice, we observed a gender difference in EPO effects in weight control. EPO treatment reduced diet-induced weight gain from 9.6 ± 1.5 to 4.2 ± 1.4 g in male mice (

Topics: Animals; Energy Metabolism; Erythropoietin; Estrogens; Female; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ovariectomy; Receptors, Erythropoietin; Sex Factors; Weight Loss

Rapid body mass loss (RBML) before competition was found to decrease hemoglobin mass (Hbmass ) in elite boxers. This study aimed to investigate the underlying mechanisms of this observation. Fourteen well-trained combat athletes who reduced body mass before competitions (weight loss group, WLG) and 14 combat athletes who did not practice RBML (control group, CON) were tested during an ordinary training period (t-1), 1-2 days before an official competition (after 5-7 days RBML in WLG, t-2), and after a post-competition period (t-3). In WLG, body mass (-5.5%, range: 2.9-6.8 kg) and Hbmass (-4.1%) were significantly (P < 0.001) reduced after RBML and were still decreased by 1.6% (P < 0.05) and 2.6% (P < 0.001) at t-3 compared with t-1. After RBML, erythropoietin, reticulocytes, haptoglobin, triiodothyronine (FT3 ), and free androgen index (FAI) were decreased compared with t-1 and t-3. An increase occurred in ferritin and bilirubin. Peak treadmill-running performance and VO2peak did not change significantly, but performance at 4-mmol lactate threshold was higher after RBML (P < 0.05). In CON, no significant changes were found in any parameter. Apparently, the significant decrease in Hbmass after RBML in combat athletes was caused by impaired erythropoiesis and increased hemolysis without significant impact on aerobic performance capacity.

Topics: Adolescent; Adult; Anaerobic Threshold; Androgens; Boxing; Erythropoiesis; Erythropoietin; Exercise; Haptoglobins; Hemoglobins; Hemolysis; Humans; Male; Martial Arts; Plasma Volume; Reticulocyte Count; Sports; Triiodothyronine; Weight Loss; Wrestling; Young Adult

Myelofibrosis (MF) is characterized by shortened survival and a greatly compromised quality of life. Weight loss and cachexia seem to be the most important factors influencing survival in patients with MF. The aim of this study was to assess the efficacy of an integrated supportive therapy in improving cachexia and MF-related symptoms.. We reported on a case of a patient with MF who presented with weight loss and cachexia associated with severe anemia, fatigue, fever, and bone pain. The circulating levels of inflammatory, oxidative stress parameters, hepcidin, and erythropoietin were evaluated and were above normal ranges. The patient was treated with a multitargeted approach specifically developed for cachexia including oral l-carnitine, celecoxib, curcumin, lactoferrin, and subcutaneous recombinant human erythropoietin (EPO)-α.. Surprisingly, after 1 y, cachexia features improved, all MF symptoms were in remission, and inflammatory and oxidative stress parameters, hepcidin, and EPO were reduced.. Because our protocol was targeted at inflammation and the metabolic state, its effectiveness may emphasize the role of inflammation in the pathogenesis of MF symptoms and demonstrates a need for the study of new integrated therapeutic strategies.

Topics: Anemia; C-Reactive Protein; Cachexia; Carnitine; Celecoxib; Curcumin; Erythropoietin; Fatigue; Ferritins; Fever; Hepcidins; Humans; Interleukin-6; Iron; Lactoferrin; Male; Middle Aged; Oxidative Stress; Patient Compliance; Primary Myelofibrosis; Quality of Life; Reactive Oxygen Species; Recombinant Proteins; Treatment Outcome; Tumor Necrosis Factor-alpha; Weight Loss

Approximately 50 % of patients with inflammatory bowel disease (IBD) suffer from anaemia, with Fe deficiency being the most common cause. CD52 monoclonal antibody (mAb) targets the cell surface CD52 and is effective in depleting lymphocytes through cytolytic effects in vivo. The aim of the present study was to investigate the therapeutic effect of anti-mouse CD52 mAb on Fe-deficient anaemia in IBD. IL-10 knockout mice (IL-10- / -) of 12 weeks with established colitis were treated with anti-mouse CD52 mAb once per week for 2 weeks. Severity of colitis, blood T lymphocytes, blood Hb, haematocrit, plasma erythropoietin (EPO), serum Fe concentration, transferrin saturation, splenic Fe stores, expression of liver hepcidin mRNA, Western blotting of the phosphorylated form of Smad1/5/8 and total Smad1 were measured at the end of the experiment. IL-10- / - mice treated with CD52 mAb showed a reduction in the percentage of CD4+ and CD4+CD45+ T cells in blood and weight loss typically associated with colonic inflammation, serum levels of EPO, the expression of liver hepcidin mRNA and total Smad1 protein, while they showed an increase in Hb concentrations, haematocrit, levels of serum Fe, transferrin saturation and splenic Fe stores. The present results indicated that anti-CD52 therapy may ameliorate Fe-deficient anaemia by reducing colonic inflammation. These findings may open novel horizons in the treatment of patients with IBD by resetting of immunological homeostasis in the gut by depleting the activated T cells in the gut mucosa.

Topics: Anemia, Iron-Deficiency; Animals; Antibodies, Monoclonal; Antigens, CD; Antigens, Neoplasm; CD4 Antigens; CD52 Antigen; Colitis; Erythropoietin; Glycoproteins; Hemoglobins; Hepcidins; Interleukin-10; Leukocyte Common Antigens; Liver; Lymphocyte Count; Mice; Mice, Inbred C3H; Mice, Knockout; RNA, Messenger; T-Lymphocytes; Weight Loss

The neuroprotective activity of recombinant human erythropoietin (r-HuEpo) sorbed on poly(butyl)cyanoacrilate nanoparticles (EPO-PBCA) and on polylactic-co-glycolic acid nanoparticles (EPO-PLGA) has been studied on Wistar rats with intracerebral post-traumatic hematoma (model of hemorrhagic stroke) (IPH-HS) in comparison to native r-HuEpo. It is established that EPO-PBCA produced a protective effect in rats after IPH-HS that was manifested by a decrease in the number of animals with neurological disorders such as circus movement, paresis, and paralysis of hind limbs; the drug also improved coordination (rotating rod test), reduced the number of lost animals, and decreased the loss weight among survived rats. In addition, EPO-PBCA optimized the research behavior of rats with IPH-HS in the open field test and prevented amnesia of passive avoidance reflex (PAR), which was caused by the IPH-HS. These effects were manifested during a two-week observation period. EPO-PLGA has a similar but much less pronounced effect on the major disorders caused by IPH-HS. The efficiency of native r-HuEpo as a neuropotective agent was insignificant and only manifested by decrease in the number of lost animals with IPH-HS.

Topics: Adsorption; Amnesia; Animals; Cerebral Hemorrhage; Disease Models, Animal; Enbucrilate; Erythropoietin; Humans; Lactic Acid; Male; Motor Activity; Nanoparticles; Neuroprotective Agents; Paralysis; Paresis; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Wistar; Recombinant Proteins; Stroke; Survival Rate; Weight Loss

Anemia in patients with COPD and its pathophysiology is an understudied issue.. In a group of 101 COPD patients (FEV(1) percentage of predicted, 37 +/- 2% [mean +/- SEM]; mean age, 61 +/- 1 years; 35% female gender), the prevalence of anemia and its relationship to body mass and weight loss, inflammatory parameters, and erythropoietin levels was determined. Data were compared to a control group (healthy persons with matched age) in order to identify potential factors that may influence the development of anemia in patients with COPD.. Anemia was diagnosed in 13 patients (hemoglobin levels < 13.5 mg/dL in male patients and < 12.0 mg/dL in female patients), which represents a prevalence of 13%. Anemic COPD patients showed elevated erythropoietin levels (41.8 +/- 25.4 U/L vs 16.3 +/- 2.9 U/L) and an increased inflammatory response compared to nonanemic patients. A significant inverse correlation of hemoglobin vs erythropoietin (r = - 0.84, p < 0.01) was observed in anemic COPD patients, but not in the nonanemic group.. Anemic COPD patients show high erythropoietin levels, which may indicate presence of erythropoietin resistance. The latter may be mediated through inflammatory mechanisms, which is typical for anemia of chronic illness.

Topics: Anemia; Body Mass Index; Erythropoietin; Female; Forced Expiratory Volume; Hemoglobins; Humans; Inflammation; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Vital Capacity; Weight Loss

Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice.. Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1-11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated.. Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss.. Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.

Topics: Adenocarcinoma; Animals; Cachexia; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Glycolysis; Hematocrit; Hemoglobins; Inhalation; Mice; Mice, Inbred BALB C; Oxygen; Recombinant Proteins; Weight Loss

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expanded CAG repeat in the HD gene. Both excitotoxicity and oxidative stress have been proposed to play important roles in the pathogenesis of HD. Since no effective treatment is available, this study was designed to explore the therapeutic potential of erythropoietin (EPO), a cytokine that has been found to prevent excitotoxicity, and to promote neurogenesis. To avoid the side effects of a raised hematocrit, we used asialoerythropoietin (asialoEPO), a neuroprotective variant of EPO that lacks erythropoietic effects in mice. R6/2 transgenic HD mice were treated with this cytokine from five to twelve weeks of age.. We provide new evidence that cell proliferation in the dentate gyrus of the R6/2 hippocampus is reduced by 50% compared to wild-type littermate controls. However, we found that the asialoEPO treatment did not affect the progression of motor symptoms, weight loss or the neuropathological changes. Furthermore, cell proliferation was not enhanced.. We conclude that the chosen protocol of asialoEPO treatment is ineffective in the R6/2 model of HD. We suggest that reduced hippocampal cell proliferation may be an important and novel neuropathological feature in R6 HD mice that could be assessed when evaluating potential therapies.

Topics: Animals; Asialoglycoproteins; Behavior, Animal; Cell Division; Cytokines; Dentate Gyrus; Disease Models, Animal; Disease Progression; Erythropoietin; Female; Huntington Disease; Male; Mice; Mice, Transgenic; Neuroprotective Agents; Phenotype; Treatment Failure; Weight Loss

Accurate information on prevalence and status of blood pressure (BP) control in hemodialysis patients is lacking. Our Hemodialysis Quality Improvement Program, sought to determine: 1) The extent and control of hypertension (HTN), 2) whether Erythropoietin (EPO) dose or intradialytic fluid loss had any effect on BP and 3) a means to follow the severity of HTN.. The pre/post mid-week dialysis BP readings of 190 patients (64+/-14.1 years, 53% males, 77% whites) were evaluated over a 3 month period. HTN was defined as BP >150/90. Hypertension was further characterized according to whether the patients had normal or elevated pre-dialysis systolic, pre-dialysis diastolic, post-dialysis systolic or post-diastolic BP readings on more than 6 of the possible 13 recordings. The average EPO dose and weight loss during dialysis was correlated with BP. To better understand the extent of HTN, systolic and diastolic pressures were separately graded from 0 to 3 and a number designated as hypertension sensitivity index (HSI) was assigned to each patient.. Of the 190 patients, 146 (76.8%) were hypertensive. 117 out of 146 hypertensive patients (80.1%) had persistent elevation of BP despite being on one or more antihypertensive medications. Most patients were on calcium channel blockers (39%) with 27% being on beta-blockers and 14% on Angiotensin converting enzyme inhibitors. There was no correlation between the number of medications used and the control of HTN. The dose of EPO also had no effect on the degree of HTN. 69.8% of all HTN was systolic. Of this, 64.7% was pre-dialysis and 35.3% post-dialysis. Multiple regression analysis demonstrated a significant correlation with loss of weight during dialysis and lowering of systolic BP (r = 0.33, p = 0.0001). The mean HSI for this population was 2.3+/-1.8.. HTN was a frequent finding in our hemodialysis population and it was controlled in only 19.9% of hypertensive patients. Most of this HTN was pre-dialysis systolic. There was a significant correlation between fluid loss during dialysis and lowering of blood pressure. The use of the HSI has proven to be helpful in differentiating type and severity of HTN.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Erythropoietin; Female; Humans; Hypertension, Renal; Male; Middle Aged; Prevalence; Renal Dialysis; Retrospective Studies; Weight Loss

The ability of combination treatment with erythropoietin (Epo) and heme to rescue hematopoietic activity in mice from the suppressive effect of azidothymidine (AZT) was determined. Exposure of mice to AZT for 5 weeks produced marked anemia, thrombocytopenia, neutropenia, and weight loss, whereas mice that received Epo and heme for 3 subsequent weeks showed significant alleviation of AZT cytotoxicity. Treatment with Epo (10 U for 5 times/week) stimulated hematopoietic recovery in the AZT-treated animals and reduced the severe anemia and thrombocytopenia by 3 weeks. Administration of a lower Epo dose (1 U Epo) resulted in only a modest retardation of AZT-induced anemia, although, when combined with heme, there was a great improvement in recovery of erythropoiesis. The combination of heme with Epo (10 U) produced the optimum response, resulting in almost normal recovery of bone marrow cellularity as well as recovery of burst-forming units-erythroid (BFU-E) and splenic hematopoietic progenitor content (colony-forming unit-spleen [CFU-S]) by the end of 3 weeks of post-AZT treatment. Treatment with heme alone markedly enhanced the recovery of BFU-E and CFU-S, as well as body weight post-AZT; however, this recovery was not to the extent seen in combination with Epo (10 U). Long-term bone marrow cultures (LTBMCs) established from mice exposed to AZT for 8 weeks showed a marked reduction in cellularity and this was completely alleviated when mice received heme and Epo (10 U) for 3 weeks after 5 weeks of AZT administration. The additive effect of heme and Epo was seen in BFU-E production, as well as in CFU-S production, in LTBMCs. Thus, heme exerts a significant protective effect on hematopoietic progenitors in vivo and may be of potential clinical use in combination with Epo to promote effective erythropoiesis in the setting of AZT therapy.

Topics: Anemia; Animals; Body Weight; Bone Marrow Cells; Cells, Cultured; Colony-Forming Units Assay; Drug Synergism; Erythropoietin; Female; Hematopoiesis; Hematopoietic Stem Cells; Heme; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neutropenia; Thrombocytopenia; Weight Loss; Zidovudine