losartan-potassium and Iron-Metabolism-Disorders

Backgroud. Anemia is one of the laboratory and clinical findings of chronic kidney diseases (CKD). The presence of anemia in patients with CKD has a wide range of clinically important consequences. Some of the symptoms that were previously attributed to reduced renal function are, in fact, a consequence of anemia. Anemia contributes to increased cardiac output, the development of left ventricular hypertrophy, angina, and congestive heart failure. According to current knowledge, anemia also contributes to the progression of CKD and is one of the factors that contribute to the high morbidity and mortality in patients with chronic renal failure and their reduced survival.. MEDLINE search was performed to collect both original and review articles addressing anemia in CKD, pathophysiology of renal anemia, erythropoiesis, erythropoietin, iron metabolism, inflammation, malnutrition, drugs, renal replacement therapy and anemia management. The present review summarized current knowledge in the field of the pathophysiology of renel anemia. Understanding the pathophysiology of anemia in CKD is crucial for the optimal treatment of anemia according to recent clinical practice guidelines and recommendation, and correct recognition of causes of resistence to treatment of erythropoietin stimulating agents (ESA).

Topics: Adult; Anemia; Erythropoiesis; Erythropoietin; Hemoglobins; Humans; Iron Deficiencies; Iron Metabolism Disorders; Renal Insufficiency, Chronic

Anemia occurs frequently in patients with chronic kidney disease (CKD), especially in the later stages, and the main etiologies are decreased production of erythropoietin (EPO) as well as iron and vitamin deficiencies. For these reasons, it is essential to detect anemia in patients with CKD and to investigate the etiology. If anemia (Hb < 100 g/l) persists after substitution of deficiencies, treatment with recombinant human erythropoietin (rHuEPO) should be considered. New guidelines (KDIGO - August 2012) have just been published by the National Kidney Foundation (NKF) for the management of anemia in patients with renal failure. This article reviews the principles and innovations in management in 2013.

Topics: Anemia; Erythropoietin; Humans; Iron Metabolism Disorders; Kidney Failure, Chronic; Models, Biological; Nephrology; Recombinant Proteins

The relationships between erythropoietin (EPO), iron, and erythropoiesis and the presence of iron-restricted erythropoiesis have important implications in anemia management. Iron-restricted erythropoiesis occurs in the presence of one or more iron deficiency syndromes: absolute iron deficiency, functional iron deficiency, and/or iron sequestration. Absolute iron deficiency is a common nutritional deficiency in women's health, pediatrics, and the elderly and is therefore an important public health problem. Functional iron deficiency occurs in patients with significant EPO-mediated erythropoiesis or therapy with erythropoiesis-stimulating agents, even when storage iron is present. Iron sequestration mediated by hepcidin is an underappreciated but common cause of iron-restricted erythropoiesis in patients with chronic inflammatory disease. The challenge for treating and laboratory-based physicians is to understand the contributory role(s) of each of these syndromes, so that the potential value of emerging and innovative pharmacologic strategies can be considered as options in patient blood management.

Topics: Aged; Antimicrobial Cationic Peptides; Child; Child, Preschool; Chronic Disease; Erythropoiesis; Erythropoietin; Female; Hepcidins; Humans; Infant; Inflammation; Iron; Iron Deficiencies; Iron Metabolism Disorders; Male; Middle Aged; Syndrome

Anemia is common in patients with cancer. The incidence and severity of anemia depend on the type and extent of the malignancy. Anemia may be the result of the malignancy itself, cancer treatment, blood losses, hemolysis or inflammatory cytokines associated with chronic disease. Anemia can have a profound impact on physical and psychosocial function and quality of life. However, in Japan, only iron supplementation and blood transfusion were available for the treatment of anemia with cancer. On the other hand, in Europe and America, erythropoietic agents such as erythropoietin and novel erythropoiesis stimulating protein (NESP) have been clinically used for anemia in patients with cancer.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Hematinics; Hemolysis; Hemorrhage; Humans; Iron Metabolism Disorders; Neoplasms; Prognosis; Recombinant Proteins

Iron sufficiency is critical for rapidly developing fetal and neonatal organ systems. The majority of iron in the third trimester fetus and the neonate is found in the red cell mass (as hemoglobin), with lesser amounts in the tissues as storage iron (e.g. ferritin) or functional iron (e.g. myoglobin, cytochromes). Iron is prioritized to hemoglobin synthesis in red cells when iron supply does not meet iron demand. Thus, non-heme tissues such as the skeletal muscle, heart and brain will become iron deficient before signs of iron-deficiency anemia. Gestational conditions that result in lower newborn iron stores include severe maternal iron deficiency, maternal hypertension with intrauterine growth retardation and maternal diabetes mellitus. Stable, very low birthweight premature infants are also at risk for early postnatal iron deficiency because they accrete less iron during gestation, grow more rapidly postnatally, are typically undertreated with enteral iron and receive fewer red cell transfusions. Conversely, iron overload remains a significant concern in multiply transfused sick preterm infants because they have low levels of iron-binding proteins and immature antioxidant systems.. The highly variable iron status of preterm infants combined with their risk for iron deficiency and toxicity warrants careful monitoring and support in the newborn and postdischarge periods.

Topics: Anemia, Iron-Deficiency; Combined Modality Therapy; Erythrocyte Transfusion; Erythropoietin; Female; Fetal Growth Retardation; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Iron Compounds; Iron Metabolism Disorders; Iron Overload; Maternal-Fetal Exchange; Perinatology; Pregnancy; Recombinant Proteins; Risk Assessment; Risk Factors; Severity of Illness Index

Topics: Anemia; Arthritis, Rheumatoid; Cytokines; Erythropoietin; Humans; Iron Metabolism Disorders; Polycythemia

High doses of iron are recommended intravenously in iron-depleted hemodialysis (HD) patients receiving recombinant erythropoietin (EPO). Iron deficiency and mainly iron overload impair cellular and humoral immune response mechanisms. Imbalances in T cell subsets are common findings in disorders of iron metabolism. The aim of this study was to evaluate the effect of iron load on peripheral blood lymphocytes subsets and on circulating cytokine levels in HD iron depleted patients, treated with EPO.. We studied 19 stable adult HD patients, 12 males, with a mean age 59 +/- 11 years and mean HD duration 24 +/- 14 months. All patients were iron deficient and were treated with unchanged EPO dose for the last 4 months before entering the study. The administered dose of iron was infused intravenously (1,000 mg iron sucrose) in 10 doses, during 10 consecutive HD sessions. Patients were screened before the commencement of the HD session on two occasions, once prior to the first dose of iron and 2 days after the 10th dose. Hematocrit (Ht), hemoglobin (Hb), iron, serum ferritin, transferrin saturation, interleukin (IL)-2, IL-4, IL-10, interferon-gamma and tumor necrosis factor-alpha were measured. Major lymphocyte subsets (CD3+, CD19+, CD4+, CD8+, CD16+/56+, CD3+CD16+CD56+) and the ratio CD4+/CD8+ were also determined by two-color immunofluorescent analysis using flow cytometry.. Hb, transferrin saturation and ferritin increased significantly at the end of the study 11.2 +/- 0.9 to 11.6 +/- 0.8 g/dl, p < 0.005, 17.5 +/- 6.9 to 23.0 +/- 10.8 %, p < 0.05, and 70 +/- 43 to 349 +/- 194 microg/l, p < 0.005, respectively. IL-2 also increased significantly 27.8 +/- 15.2 to 38.9 +/- 12.8 pg/ml, p < 0.05. After iron load there was no significant change to the major lymphocyte subsets examined but a significant increase of the percentage and number of T lymphocytes with positive natural killer receptors (NKR+ T) cells was observed, 5.1 +/- 3.7% to 6.3 +/- 3.46%, p < 0.05, and 76.4 +/- 40 to 101.5 +/- 48 cells/microl, p < 0.005, respectively.. Iron load in iron-deficient EPO-treated HD patients did not produce any changes in major lymphocyte subsets in peripheral blood, but it resulted in a significant increase of NKR+ T cells, a subpopulation important for local immune responses. Iron load for a relatively short period improved anemia of HD patients and influenced the levels of the circulating IL-2, which may regulate factors affecting the survival of patients.

Topics: Adult; Cytokines; Erythropoietin; Female; Humans; Iron; Iron Metabolism Disorders; Lymphocytes; Male; Middle Aged; Renal Dialysis

Although erythropoietin (EPO)-hyporesponsive anemia in hemodialysis patients most commonly results from iron deficiency, the contributory role of chronic inflammation and oxidative stress in its pathogenesis is poorly understood. We conducted an open-label prospective study to assess the effect of vitamin C, an antioxidant, on EPO-hyporesponsive anemia in hemodialysis patients with unexplained hyperferritinemia.. Forty-six of 262 patients in an inner-city hemodialysis center met the inclusion criteria (administration of intravenous iron and EPO for > or = 6 months at a dose > or = 450 U/kg/wk, average 3-month hemoglobin [Hb] level < or = 11.0 g/dL [< or = 110 g/L], ferritin level > or = 500 ng/mL (microg/L), and transferrin saturation [TSAT] < or = 50%). Patients were excluded if they had a clear explanation for the EPO hyporesponsiveness. Four patients refused to participate. The remaining patients were randomly assigned; 20 patients to receive standard care and 300 mg of intravenous vitamin C with each dialysis session (group 1) and 22 patients to receive standard care only (group 2). Study duration was 6 months. During the study, 1 patient from group 1 was removed (upper gastrointestinal bleeding) from final analysis. Monthly assessment included Hb level, mean corpuscular volume, iron level, iron-binding capacity, ferritin level, TSAT, and Hb content in reticulocytes. In addition, biointact parathyroid hormone, aluminum, C-reactive protein (CRP), and liver enzymes were measured every 3 months.. Age, sex, race, and time on dialysis therapy were similar in both groups. At 6 months, Hb levels significantly increased from 9.3 to 10.5 g/dL (93.0 to 105.0 g/L) in group 1, but not group 2 (9.3 to 9.6 g/dL [93.0 to 96.0 g/L]; P = 0.0001). Similarly, TSAT increased from 28.9% to 37.3% in group 1, but not group 2 (28.7% to 29.3%; P = 0.0001). EPO dose (477 to 429 versus 474 to 447 U/kg/wk), iron-binding capacity (216 to 194 versus 218 to 257 microg/dL [38.7 to 34.7 versus 39 to 46 micromol/L]), and CRP level (2.8 to 0.9 versus 2.8 to 2.2 mg/dL) decreased significantly in group 1, but not in controls. Changes in Hb content in reticulocytes and ferritin level also were statistically significant in group 1. There was no change in biointact parathyroid hormone levels. Although serum iron levels and intravenous iron doses changed within each group, changes were equal between the 2 groups.. In hemodialysis patients with refractory anemia and hyperferritinemia, vitamin C improved responsiveness to EPO, either by augmenting iron mobilization from its tissue stores or through antioxidant effects.

Topics: Adult; Anemia; Antioxidants; Ascorbic Acid; Erythropoietin; Female; Ferritins; Humans; Injections, Intravenous; Iron Metabolism Disorders; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

The substantial risk of iron overload is not routinely monitored in most of the neonatal intensive care units (NICUs) in Japan; however, blood transfusion is an essential strategy for successfully treating preterm low-birth-weight infants.. The aim of this study was to investigate the iron status and clinical features of infants with a birth weight of <1,500 g, i.e. very-low-birth-weight infants (VLBWIs).. This prospective observational study enrolled 176 (82.6%) patients from a total of 213 VLBWIs admitted to our NICU from 2009 to 2014. Clinical information was collected including maternal records and infant morbidity and treatment. Management strategies including enteral iron supplementation, erythropoietin administration and blood transfusion were allowed according to the consensus in Japan. The hematological status was surveyed from birth to 12 postnatal weeks of age. The iron status was determined according to serum iron, unbound iron-binding capacity and serum ferritin. The definition of hyperferritinemia was set as a value of ≥500 ng/ml.. Twenty-four (13.6%) infants displayed hyperferritinemia. A multiple logistic analysis selected 3 associated factors of hyperferritinemia: surgical ligation for patent ductus arteriosus, sepsis and moderate or severe states of bronchopulmonary dysplasia. We also verified that the value of ferritin was significantly correlated with those of aspartate transaminase, creatine kinase and C-reactive protein according to a multilinear regression analysis. After excluding the ferritin data of these outliers, we did not observe any factors associated with hyperferritinemia.. Hyperferritinemia might be associated with oxygen radical diseases and susceptibility to infection.

Topics: Birth Weight; Bronchopulmonary Dysplasia; C-Reactive Protein; Ductus Arteriosus, Patent; Erythropoietin; Female; Ferritins; Gestational Age; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Iron Metabolism Disorders; Iron Overload; Japan; Logistic Models; Male; Multivariate Analysis; Prospective Studies; Sepsis

Enhanced erythropoietic drive and iron deficiency both influence iron homeostasis through the suppression of the iron regulatory hormone hepcidin. Hypoxia also suppresses hepcidin through a mechanism that is unknown. We measured iron indices and plasma hepcidin levels in healthy volunteers during a 7-day sojourn to high altitude (4340 m above sea level), with and without prior intravenous iron loading. Without prior iron loading, a rapid reduction in plasma hepcidin was observed that was almost complete by the second day at altitude. This occurred before any index of iron availability had changed. Prior iron loading delayed the decrease in hepcidin until after the transferrin saturation, but not the ferritin concentration, had normalized. We conclude that hepcidin suppression by the hypoxia of high altitude is not driven by a reduction in iron stores.

Topics: Adult; Altitude; Antimicrobial Cationic Peptides; beta-Thalassemia; Case-Control Studies; Erythropoiesis; Erythropoietin; Ferritins; Gene Expression Regulation; Growth Differentiation Factor 15; Hepcidins; Homeostasis; Humans; Hypoxia; Iron; Iron Metabolism Disorders; Iron, Dietary; Transferrin