losartan-potassium and Infections

Cardiovascular disease and infections are directly or indirectly associated with an altered immune response, which leads to a high incidence of morbidity and mortality, and together, they account for up to 70% of all deaths among patients with chronic kidney dysfunction. Impairment of the normal reaction of the innate and adaptive immune systems in chronic kidney disease predisposes patients to an increased risk of infections, virus-associated cancers, and a diminished vaccine response. On the other hand, an abnormal, exaggerated reaction of the immune systems can also occur in this group of patients, resulting in increased production and decreased clearance of proinflammatory cytokines, which can lead to inflammation and its sequelae (eg, atherosclerotic cardiovascular disease). Epigenetically, modifications in hematopoietic stem cells involving a shift from lymphoid to myeloid cell lineage may underlie uremia-associated immunological senescence, which is not reversed by renal replacement therapy, including kidney transplantation. Measures aimed at attenuating the immune abnormalities in chronic kidney disease/end-stage renal disease should be an area of focused research as this could potentially lead to a better understanding and, thus, development of therapies that could reduce the disastrously high death rate in this patient population. The aim of the present article is to review the characteristics, causes, and mechanisms of the immune dysfunction related to chronic kidney disease.

Topics: Adaptive Immunity; Calcitriol; Calcium; Epigenesis, Genetic; Erythropoietin; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Gastrointestinal Microbiome; Hematopoietic Stem Cells; Humans; Immunity, Innate; Immunocompromised Host; Immunosenescence; Infections; Inflammation; Iron; Oxidative Stress; Parathyroid Hormone; Renal Insufficiency, Chronic; Renal Replacement Therapy; Renin; Renin-Angiotensin System; Vitamin D

Kidney transplantation represents a renal replacement therapy for end-stage renal failure, with outcomes improving from year to year. With the improved survival prognosis, treatment of complications of chronic kidney disease after transplantation is becoming increasingly important. In particular, posttransplantation anemia (PTA) is often protracted, which could be related to a variety of factors, including the renal function status, graft rejection episodes, and infectious causes. PTA occurs in about 30-40% of transplant recipients, and is known to affect the function of the transplanted kidney as well as patient survival. Early PTA is associated with a risk of death and cardiovascular disorders, however, during this phase, priority is given to the appropriate maintenance of immunosuppression rather than to the treatment of anemia. Maintenance-phase PTA exerts a strong influence on the survival, prognosis of the transplanted kidney, quality of life, etc. Unlike the disease state and treatment of usual renal anemia, it has been suggested that PTA may possibly reflect the functional state of the transplanted kidney. Therefore, it has been suggested that proper renal function may be maintained by ensuring a normal hemoglobin level in kidney transplant recipients. Proper management of PTA could be expected to be associated with an improved prognosis of the transplanted kidney and improved patient survival in kidney transplant recipients. It is advisable to provide appropriate treatment by setting target levels in accordance with the dialysis vintage, primary disease, cardiovascular complications, and kidney transplant function and delineation of the transplant recipient characteristics.

Topics: Anemia; Anemia, Iron-Deficiency; Anti-Bacterial Agents; Antiviral Agents; Blood Transfusion; Erythropoietin; Graft Rejection; Hematinics; Hemolysis; Humans; Immunosuppressive Agents; Infections; Iron Compounds; Kidney Failure, Chronic; Kidney Transplantation; Neoplasms; Sex Factors; Time Factors

Iron Deficiency Anaemia (IDA) has been shown to be the most common cause of anaemia worldwide. It is accepted that people with chronic kidney disease (CKD) develop anaemia as their kidney function declines.. To better understand IDA in CKD, it is necessary to appreciate the normal iron metabolism and utilisation of iron and how these processes can be disordered in patients with CKD. The problems related to infection / inflammation and oxidative stress are examined. Whilst National and international guidelines recommend specific tests for IDA, these and alternative tests are reviewed.. Whilst iron supplementation is necessary for CKD patients with IDA, iron metabolism and utilisation can be affected by factors such as infection or inflammation. Iron is essential element for all life, it can be toxic to cells through the process of oxidative stress. The recommended tests for IDA may be affected by factors such as infection and inflammation. Alternative tests are available, which may be a more accurate indicator of IDA as they are not affected by external factors.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Guideline Adherence; Hepcidins; Humans; Infections; Inflammation; Iron; Kidney Failure, Chronic; Oxidative Stress; Reference Values

Anemia of chronic disease (ACD) is a mild to moderate anemia seen with many infections and inflammatory disorders. These patients have low serum iron, but high serum ferritin levels. As for the pathogenesis of ACD, previous studies have reported several abnormalities, such as insufficient EPO production, impaired growth response of erythroid progenitors to EPO, and shortened survival of erythrocytes, due to the inflammatory cytokines. However, recent analyses have clearly shown that hepcidin, of which expression is induced by inflammatory cytokines such as IL-1beta and IL-6, suppresses the expression of the iron transporter, ferroportin-1, thereby inhibiting the absorption of iron from the duodenum, the release of iron from the reticulo-endothelial system. So, the abnormal expression of hepcidin alone may be able to explain the unique iron metabolism in ACD.

Topics: Anemia; Antimicrobial Cationic Peptides; Cation Transport Proteins; Chronic Disease; Cytokines; Duodenum; Erythroid Precursor Cells; Erythropoietin; Ferritins; Hepcidins; Humans; Infections; Inflammation; Inflammation Mediators; Intestinal Absorption; Iron; Iron Deficiencies

Pregnancy, although rare in the patient with end-stage renal disease, is not uncommon in the transplant recipient. Physicians taking care of transplant recipients must be able to inform patients about the potential risks of pregnancy in this setting. The patient and her partner must know that the risks associated with pregnancy increase with worsening kidney function and hypertension. Current consensus opinion is that pregnancy can be relatively safely undertaken by 1 year after transplant if the patient has had no rejections during the year, allograft function is adequate, there are no infections that could affect the fetus, the patient is not taking teratogenic medications, and immunosuppressive medication dosing is stable. Consideration must be given to immunosuppression during pregnancy both with respect to the specific agents as well as the level of dosing. None of the medications are FDA category A; all are B or higher. Part of planning for pregnancy should include an evaluation of immunosuppression medication and a plan to modify the regimen prior to conception if its use may be risky for the developing fetus. Rejection can occur during a kidney transplant, so maintaining adequate immunosuppression is important. Other issues that need to be managed when caring for a pregnant transplant patient include: potential for infection (urinary tract infections are very common), hypertension, and anemia. The type of delivery, posttransplant contraception, and breast-feeding also need to be addressed.

Topics: Anemia; Counseling; Erythropoietin; Female; Graft Rejection; Humans; Hypertension; Immunocompromised Host; Immunosuppressive Agents; Infections; Kidney Failure, Chronic; Kidney Transplantation; Patient Care Team; Preconception Care; Pregnancy; Pregnancy Complications; Recombinant Proteins; Time Factors

Diabetes as the dominant cause of ESRD is also the major cause of renal anaemia. However, most patients with diabetic kidney disease will succumb to co-morbid vascular disease or heart failure before developing severe renal impairment. In these patients, anaemia is also common finding, with a 2-3 times greater prevalence and earlier onset than in patients with renal impairment from other causes. We have recently shown that at least one in five outpatients with type 1 or type 2 diabetes in tertiary referral clinics have anaemia, in whom it constitutes a significant additional burden. Impaired renal erythropoietin release in response to declining haemoglobin levels appears to be the major contributor to anaemia in diabetes. This may be due to the predominance of damage to cells and vascular architecture of the renal tubulointerstitium associated with diabetic nephropathy that may be apparent, like albuminuria, before demonstrable changes in renal function. In addition, systemic inflammation, autonomic neuropathy and reduce red cell survival may also compound anaemia in diabetes. While anaemia may be considered a marker of diabetic kidney disease, reduced haemoglobin levels, even within the normal range, identify diabetic patients with an increased risk of hospitalisation and mortality. Anaemia may also be significant in determining the outcome of heart failure and hypoxia-induced organ damage in patients with diabetes. Upcoming studies will determine whether correction of anaemia in diabetes will lead to improved outcomes in these patients.

Topics: Anemia; Blood Pressure; Diabetes Complications; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Erythrocytes; Erythropoietin; Glomerular Filtration Rate; Hematopoiesis; Humans; Infections; Kidney; Microcirculation; Prevalence; Wound Healing

The importance of iron in the manufacture of erythrocytes is self-evident. In recent years, the treatment of anaemia of end-stage renal disease with recombinant human erythropoietin (epoetin) has been optimized by adequate iron supply. Intravenous therapy with dextran-free iron compounds has become the ideal and necessary companion of epoetin therapy. Anxiety has been expressed by clinicians and researchers over the impact of excess levels of iron following i.v. administration. Their concerns have included the potential for short-term side effects such as anaphylactic reactions and response to 'free iron'. Long-term concerns have included the possibility of increased infection, oxidative stress and cardiovascular disease with higher levels of iron. The literature also implies that i.v. iron could be a 'two-edged sword', i.e. on the one hand, it optimizes epoetin therapy, while on the other, it puts the patient at greater risk of other complications. This review assesses the evidence for these concerns and concludes that i.v. therapy with dextran-free iron compounds, such as iron sucrose, optimizes epoetin therapy with no direct evidence of any short-term or long-term complications.

Topics: Anemia; Chemotherapy, Adjuvant; Drug Hypersensitivity; Erythropoietin; Ferritins; Heart Diseases; Hematinics; Humans; Infections; Infusions, Intravenous; Iron Compounds; Kidney Failure, Chronic; Oxidative Stress; Recombinant Proteins

Recent epidemiologic studies show that iron deficiency occurs in the vast majority of patients with chronic kidney disease (CKD). In patients with CKD, increased iron losses and, to a lesser extent, poor oral absorption, can lead to iron-deficiency anemia. Correction of iron-deficiency anemia is preferable by the oral route, however, data on oral iron use are limited in this population. In CKD patients, parenteral iron administered with recombinant human erythropoietin (rHuEpo), is the best potential option for the correction of anemia. Nondextran iron preparations are preferable because of a reduced incidence of serious adverse events. Parenteral iron in CKD patients may not be entirely innocuous and, although commonly used, have not received Food and Drug Administration approval for use in this patient population. Exposure to intravenous (IV) iron may lead to oxidative stress, renal injury, infection, cardiovascular disease, and osteomalacia. Studies are needed to confirm the existence and magnitude of these complications. The current data suggest that the overall risk-benefit ratio favors use of IV iron when compared with untreated or partially treated iron-deficiency anemia.

Topics: Anemia, Iron-Deficiency; Clinical Trials as Topic; Erythropoietin; Humans; Infections; Iron; Kidney Failure, Chronic; Oxidative Stress; Recombinant Proteins

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Critical Care; Erythropoietin; Hemodilution; Humans; Infections; Transfusion Reaction

The use of hematopoietic growth factors has increased rapidly during the last decade. Among the growth factors available, erythropoietin (EPO) was the first growth factor to be used clinically. To date, EPO has shown activity in the treatment of the tumor-associated anemia and for correction of tumor hypoxia, however, when compared with transfusion of erythrocytes EPO treatment did not significantly prolong survival in cancer patients in any published study so far. Recently, novel extramedullary EPO receptors have been identified leading to a better understanding of the molecular mechanisms of action of EPO. Results from these experiments and from several clinical studies suggest that EPO treatment may be beneficial for patients with (chronic) infections (HIV, inflammatory bowel disease, septic episodes) and for treatment of the fatigue syndrome following cancer chemotherapy. In addition, EPO may also improve stem cell engraftment following high-dose chemotherapy and can increase survival rates of patients with aplastic anemia and myelodysplastic syndrome. Currently, new EPO derivatives, synthetic fusion proteins and gene therapeutic studies are under clinical investigation suggesting that the EPO-induced effects may be increased significantly by these agents in the future.

Topics: Anemia, Aplastic; Chronic Disease; Erythropoietin; Fatigue; Genetic Therapy; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; HIV Infections; Humans; Infections; Myelodysplastic Syndromes; Receptors, Erythropoietin; Recombinant Proteins

There are a number of problems with allogeneic blood transfusion. Some of these problems are defined and can be quantified, such as the problem of rising cost or the risk of viral infection, but some of the problems are not well defined and it is only outcome data that point to allogeneic blood transfusion contributing to patient mortality and morbidity. Autotransfusion includes any technique in which the patient's own blood is collected, processed and stored, followed by reinfusion when circumstances dictate. In the perioperative period of cardiac surgery, a number of techniques are recognized as useful in this context. Preoperative autologous donation, with or without erythropoietin supplementation, intraoperative acute normovolaemic haemodilution, intraoperative cell salvage, postoperative cell salvage (reinfusion of shed mediastinal blood) and platelet rich plasmapheresis are all techniques which are used with more or less enthusiasm to reduce the need for an allogeneic blood transfusion. Modification of the priming technique of the cardiopulmonary bypass circuit using an autologous blood prime is included in this review even though it does not fall strictly within the definition of autotransfusion. Although autotransfusion is not the answer to every problem, there is no doubt that it should play a significant part in the strategy of blood conservation.

Topics: Blood Loss, Surgical; Blood Preservation; Blood Transfusion; Blood Transfusion, Autologous; Cardiac Surgical Procedures; Cost-Benefit Analysis; Costs and Cost Analysis; Elective Surgical Procedures; Equipment Design; Erythropoietin; Hemodilution; Humans; Infections; Intraoperative Care; Length of Stay; Mediastinum; Multicenter Studies as Topic; Patient Selection; Plasmapheresis; Platelet Transfusion; Transfusion Reaction; United Kingdom

When used as the sole source of transfused blood, the principal advantage of autologous blood transfusion is the avoidance of transmission of infectious agents and the avoidance of the purported adverse immunomodulatory effects of allogeneic transfusion. In the 1990s, however, the risks of transfusion-transmitted diseases have been greatly reduced, and estimates of the cost-effectiveness of pre-operative autologous blood donations now vary between 2470 dollars and 3,400,000 dollars per quality-adjusted year of life saved, depending on assumptions about the existence and magnitude of any adverse immunomodulatory effects of allogeneic transfusion. There is a paucity of randomized controlled trials evaluating the clinical outcomes and the cost-effectiveness of autologous transfusion procedures, and this situation is unlikely to change in the near future because of the difficulties in conducting such trials. This chapter reviews the available evidence on the efficacy, safety and cost-effectiveness of the three common autologous transfusion procedures, that is, pre-operative autologous blood donation, acute normovolaemic haemodilution, and intra-operative and post-operative blood recovery.

Topics: Blood Donors; Blood Group Incompatibility; Blood Specimen Collection; Blood Transfusion, Autologous; Cost-Benefit Analysis; Erythropoietin; Hemodilution; Humans; Infections; Intraoperative Period; Preoperative Care; Recombinant Proteins

Iron deficiency is the most frequently encountered cause of suboptimal response to recombinant human erythropoietin (rHuEPO). Carefully assessing iron status is of paramount importance in chronic renal failure patients prior to or during rHuEPO therapy. Because there is great need for iron in the EPO-stimulated erythroid progenitors, it is essential that serum ferritin and transferrin saturation levels should be maintained over 300 microg/liter and 30%, respectively. Investigators have shown that oral iron is unlikely to keep pace with the iron demand for an optimal rHuEPO response in uremics. Therefore, patients with iron deficiency will always require intravenous iron therapy. The early and prompt iron supplementation can lead to reductions in rHuEPO dose and hence cost. After the iron deficiency has been corrected or excluded, we must remember all of the possible causes of hyporesponsiveness in every rHuEPO-treated patient. As dose requirements vary, it is not clear which dose of rHuEPO causes this hyporesponsiveness. However, if the patient with iron repletion does not respond well after the induction period, the major causes blunting the response to rHuEPO should be investigated. Most factors are reversible and remediable, except resistant anemia associated with hemoglobinopathy or bone marrow fibrosis, which requires a further increase in the rHuEPO dose. By means of early detection and correction of the possible causes, the goal of increasing therapeutic efficacy can be achieved. Iron overload may lead to an enhanced risk for infection, cardiovascular complication, and cancer. Over-treatment with iron should be avoided in dialysis patients, despite the fact that the safe upper limit of serum ferritin to avoid iron overload is not clearly defined. On the other hand, functional iron deficiency may develop even when serum ferritin levels are increased. Controversy remains as to whether intravenous iron therapy can overcome this form of hyporesponsiveness in iron-overloaded patients. Moreover, a treatment option of iron supplementation is not warranted in these patients, as the potential hazards of iron overload will be worsened. We demonstrated that the mean hematocrit significantly increased from 25.1+/-0.9% to 31+/-1.2% after eight weeks of intravenous ascorbate therapy (300 mg three times a week) in 12 hemodialysis patients with serum ferritin levels of more than 500 microg/liter. The enhanced erythropoiesis paralleled with a rise in transferrin sa

Topics: Aluminum; Anemia; Erythropoietin; Hemoglobinopathies; Hemolysis; Humans; Infections; Inflammation; Iron; Iron Deficiencies; Iron Overload; Kidney Failure, Chronic; Recombinant Proteins; Thalassemia

Recombinant epoetin therapy and correction of the chronic anemia of renal failure have greatly reduced the number of red cell transfusions and hence the propensity to iron overload. The majority of HD patients require intravenous iron therapy to achieve the hematocrit levels that correspond to improved outcome measures. Although the short-term benefits of intravenous iron have been clearly defined, the long-term risks of intravenous iron are less well-defined. Iron overload before the availability of epoetin constituted a serious problem; our review of the literature does not decisively conclude that these patients had more serious bacterial infections or increased mortality when compared with their non-iron overloaded counterparts, unless chronic transfusion-related hepatic disease was superimposed. Specifically, no data unequivocally confirm that iron overload from parenteral iron contributes to all-cause patient morbidity or mortality. Furthermore, therapy that maintains intravenous iron optimal iron stores and replaces iron losses associated with the dialytic procedure does not engender iron overload in the carefully monitored patient. Optimized anemia therapy in ESRD requires individualized and specific application of epoetin and iron for each patient, and significant cost savings can result from such a strategy. Prospective studies are clearly necessary to define those parameters that reflect adequacy of iron storage in renal failure patients. We should develop alternative means of iron delivery and develop monitors that accurately discriminate between patients who will respond to additional iron therapy and those who will not. Whether ferritin should be supplanted by another parameter and whether iron itself poses an increased risk to those patients it has so beneficially served are issues that must be resolved. Until these answers are known, the importance of carefully crafted iron therapy cannot be overstated.

Topics: Anemia; Coronary Disease; Erythropoietin; Female; Free Radicals; Humans; Infections; Injections, Intravenous; Iron; Iron Deficiencies; Kidney Failure, Chronic; Male; Recombinant Proteins; Risk Factors; Safety; Transferrin

Infectious and inflammatory disorders cause a disturbance in iron metabolism that leads to a sequestration of iron in the reticuloendothelial (R-E) system and a sometimes sharp and sudden decline in red blood cell indices. Underlying inflammatory conditions can decrease responsiveness to Epoetin alfa in dialysis patients and complicate anemia management. Understanding the possible infectious and inflammatory etiologies that can affect enemia management is essential to enhancing the nursing care of dialysis patients. Nurses caring for patients receiving Epoetin alfa must be aware of the possible effects of these conditions and know how to assess, detect, intervene, and evaluate factors that detract from an optimal erythropoietic response.

Topics: Aged; Anemia; Erythropoietin; Humans; Infections; Inflammation; Kidney Failure, Chronic; Male; Nursing Assessment; Renal Dialysis

The data on the relationship between iron deficiency and infection are conflicting. Some researchers conclude that mild iron deficiency is beneficial for immunity, whereas others contend that any deficit is not good for immunity. Additionally, infection or inflammation generate anemia and profound changes in iron metabolism mediated by cytokines. These changes are important confounders to consider in assessments of iron status.

Topics: Anemia, Iron-Deficiency; Cytokines; Erythropoietin; Humans; Infections; Iron

Topics: Anemia; Chronic Disease; Erythrocyte Count; Erythropoiesis; Erythropoietin; Humans; Infections; Kidney Failure, Chronic; Neoplasms; Rheumatic Diseases

Pediatricians should understand that the anemia of inflammation is second only to iron deficiency in overall incidence. When evaluating a child for mild to moderate anemia, one should always consider hemolytic anemia, both immune and congenital, and blood loss. Careful scrutiny of the peripheral blood smear is always helpful and can assist in minimizing expensive and unnecessary evaluations. When the anemia of inflammation is suggested by history or physical examination and the CBC reveals a normocytic, or possibly microcytic, mild to moderate anemia with a normal peripheral blood smear, it is prudent to not embark on an extensive evaluation for the anemia but instead wait for the inflammation to resolve. This may take as many as 3 months, depending on the degree of inflammation. Because the anemia resolves with subsiding inflammation, it is best to avoid treatment with iron or RBC transfusions. More studies need to be performed concerning the pathogenesis of the anemia of acute inflammation in children and the best course of treatment, if needed. The role of erythropoietin in the treatment of this form of anemia, though promising in some adult models of inflammation, awaits exploration in pediatric patients.

Topics: Adult; Anemia; Anemia, Hemolytic; Cytokines; Diagnosis, Differential; Erythropoietin; Humans; Infant; Infections; Inflammation

Three hematopoietic growth factors, recombinant human granulocyte-macrophage colony-stimulating factor, recombinant human granulocyte colony-stimulating factor and erythropoietin, which are commonly used in other clinical situations are being increasingly studied in the setting of allogeneic marrow transplantation. Major questions being addressed are: 1) can administration of growth factors post-transplant accelerate hematopoietic recovery, 2) are growth factors of use in the treatment of patients with poor graft function or graft failure, 3) can growth factor mobilized peripheral blood stem cells be used as a substitute for allogeneic marrow and 4) is there a role for the use of growth factors in the treatment of patients with specific types of infection post-transplant? This review will discuss where we are in answering these four questions.

Topics: Bone Marrow Transplantation; Clinical Trials as Topic; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Humans; Infections; Recombinant Proteins; Transplantation, Homologous

The anemia associated with chronic infectious, inflammatory, and malignant diseases is characterized by a blunted erythropoietin response; for any given decrease in hemoglobin or hematocrit, the increase in serum or plasma erythropoietin is less than would be found in an equally anemic patient with iron deficiency. This observation provides a rationale for the use of recombinant human erythropoietin in the treatment of the anemia in these diseases. During the past year, new information has been reported on the pathophysiology of erythropoiesis in chronic infectious, inflammatory, and neoplastic diseases, and on the use of recombinant human erythropoietin for this anemia. This article reviews these developments.

Topics: Anemia; Chronic Disease; Clinical Trials as Topic; Erythropoietin; Humans; Infections; Inflammation; Neoplasms; Recombinant Proteins

Clinical usefulness of cytokines in cancer treatment has been described. Cytokines presently used in clinical practice are IFNs, IL-2, and hematopoietic growth factors. IFNs and IL-2 used with an expectation of direct antitumor effect of these cytokines have been proven to be specifically effective against certain types of tumors. Hematopoietic growth factors have been used as the adjuvant drugs in cancer treatment and proven to be effective against neutropenia and associated infections after chemotherapy and bone marrow transplantation. Future development of new cytokines and trials on the combination among cytokines and cytokines with chemotherapeutic agents, will promote the usefulness of cytokines in cancer treatment.

Topics: Antineoplastic Agents; Bone Marrow Transplantation; Colony-Stimulating Factors; Erythropoietin; Humans; Infections; Interferons; Interleukin-2; Neoplasms; Neutropenia; Recombinant Proteins

We review data concerning site and regulation of erythropoietin (EPO) production, its effects on target tissue, routes of administration and clinical applications. In the anaemia of chronic renal failure (ACRF) treatment with recombinant human erythropoietin (r-Hu-EPO) has been shown to be effective in both improvement of the anaemia and increase in quality of life. In the anaemia of chronic disease (ACD), associated with various malignant, infectious and inflammatory disorders, many investigators have demonstrated an inappropriately low EPO response to anaemia. Therapeutic trials in patients with ACD mostly lacked sufficient numbers of patients for evaluation of the effects. The results obtained from some studies in AIDS and rheumatoid arthritis and the effect on the number of units of autologous blood obtained from patients planned for elective surgery are encouraging, however. Adverse reactions of r-Hu-EPO treatment are mainly confined to the ACRF population and include hypertension, shunt thrombosis and pain at the injection site. The exact mechanism of action of EPO is not yet fully understood. Large scale clinical trials are required to establish its effects on both the anaemia and quality of life in anaemias other than ACRF.

Topics: Anemia; Chronic Disease; Clinical Protocols; Clinical Trials as Topic; Drug Administration Schedule; Erythropoietin; Humans; Infections; Inflammation; Kidney Failure, Chronic; Neoplasms

The emergence of the acquired immunodeficiency syndrome (AIDS) has fueled concerns of both physicians and their patients about safety of blood transfusions. Although AIDS has generated the most fear, the risk today is extremely remote (1/60.000 units of blood). The risk of transmitting infectious disease by homologous transfusion is decreasing, as more donor screening and testing measures are implemented. The blood supply is safer that at any time, but small transfusion risks exist. The most common problems associated with transfusions are temporary: one in 100-300 recipients will experience fever or rash. The biggest problem is a mismatch of the well-known ABO blood groups and once in every 100-400.000 transfusions the hemolytic reaction is fatal. Viral hepatitis is another serious and important risk. At present hepatitis seems to strike between 1 and 3 percent of transfusion recipients. Most, if not all, of transfusion-associated hepatitis cases are caused by hepatitis C virus. Cytomegalovirus can cause primary infection, reactivation or reinfection by transfusion. Immunosuppressed patients are more likely to develop more severe disease. Epstein-Barr virus does not seem to cause significant post-transfusion disease. Bacterial or protozoal infections are an infrequently encountered adverse effect of transfusion. However, some clinical cases document the potential hazard of blood components as a vector for bacteria or protozoa. Homologous blood transfusion down-regulates some immune functions. Host defences against malignancy and infection may in some instances be severely compromised by transfusions of homologous blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Adult; Blood Donors; Blood Transfusion, Autologous; Deamino Arginine Vasopressin; Epoprostenol; Erythropoietin; Female; Graft vs Host Disease; Hemodilution; Hepatitis, Viral, Human; Humans; Infant, Newborn; Infections; Male; Pregnancy; Prognosis; Protozoan Infections; Risk Factors; Transfusion Reaction

The currently available radioimmunoassay for erythropoietin (Epo) using recombinant reagents is an accurate, reproducible, sensitive and specific assay which can be used to identify whether lack of Epo is contributing to anemia and, by extension, whether therapy with recombinant Epo might be appropriate. Elevation of the serum Epo level with anemia suggests that a marrow abnormality is the cause of the anemia, while a "high" Epo level in a non-anemic or plethoric patient suggests the presence of hypoxia or autonomous Epo production. Liver disease can elevate the serum Epo level, while modest degrees of anemia do not affect it appreciably. The lowest Epo levels occur in polycythemia vera, but in a particular patient this finding is not completely diagnostic.

Topics: Anemia, Hemolytic; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature; Infections; Inflammation; Neoplasms; Polycythemia; Pregnancy; Radioimmunoassay

Renal dysfunction gives rise to a variety of hematologic disturbances, including anemia, leukocyte dysfunction, and coagulopathy. The anemia of renal failure has been attributed to a relative deficiency of erythropoietin, but contributing factors include an absolute deficiency of iron or folate. Other contributing factors include heavy metal toxicity, blood loss, and hemolysis. The treatment of the anemia of renal disease has advanced with the development of recombinant human erythropoietin. At doses from 15-500 micrograms/kg triweekly in selected patients, normalization of hemoglobin is presently possible. Transfusion may still have a role in patients with renal disease, although more as preconditioning for renal transplantation. In non-HLA matched transplantation, donor-specific transfusion, as well as immunosuppressives, may exert some benefit in graft survival. The coagulopathy of renal disease consists of an acquired qualitative platelet defect best remedied by dialysis but also treated successfully by cryoprecipitate or DDAVP. Infectious complications of uremia include diminished leukocyte chemotaxis, phagocytosis, and bactericidal activity. Cell-mediated immune defects and hypogammaglobulinemia have also been described. The pathophysiology involved in the protean hematologic manifestations of uremia are discussed; additionally, we describe therapeutic recommendations to deal with anemia, bleeding and infectious complications of renal failure.

Topics: Anemia; Blood Platelet Disorders; Blood Transfusion; Erythropoiesis; Erythropoietin; Humans; Infections; Kidney Failure, Chronic; Recombinant Proteins

Pure red cell aplasia is a selective aplasia of the marrow erythroid cells. Unlike aplastic anemia, the marrow has a normal cellularity and the patients generally have normal leukocyte and platelet blood counts. The congenital form of the disease occurs in the firlst 1 1/2 years of life and is often responsive to corticosteroids. The acquired form may be secondary to infections, drugs, chemicals, or hemolytic anemia (aplastic crisis). In these cases it is often acute and self-limited with cessation of the infection or drug ingestion. It may also be secondary to systemic lupus erythematosus, rheumatoid arthritis, acute severe renal failure, severe nutritional deficiency, or diverse neoplasms, and may remit with treatment of the primary condition. When a thymoma is present, it should be resected since a remission is produced in 29 per cent of these patients. The remaining patients have an acquired primary form of the disease that tends to be chronic and in some cases may have an immune pathogenesis. A cytotoxic immunoglobulin inhibitor of the marrow erythroid cells or erythropoietin has been described and these patients may respond to prednisone and/or to cytotoxic immunosuppressive drugs such as cyclophosphamide and 6-mercaptopurine. Pure red cell aplasia appears to be more common than the literature has revealed and has stimulated much investigation into an immune pathogenesis for marrow failure.

Topics: Acute Kidney Injury; Anemia, Aplastic; Antilymphocyte Serum; Arthritis, Rheumatoid; Blood Cell Count; Blood Transfusion; Cyclophosphamide; Deficiency Diseases; Erythropoietin; Humans; Immune System Diseases; Infections; Lupus Erythematosus, Systemic; Mercaptopurine; Prednisone; Remission, Spontaneous; Splenectomy; Thymoma; Thymus Neoplasms

Topics: Anemia; Anemia, Hypochromic; Anemia, Sideroblastic; Animals; Arthritis, Rheumatoid; Bone Marrow; Chronic Disease; Copper; Disease Models, Animal; Endotoxins; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Freund's Adjuvant; Hematocrit; Humans; Infections; Iron; Mononuclear Phagocyte System; Neoplasms; Porphyrins; Protein Binding; Rats; Transferrin

To know the variations of serum transferrin receptor (sTfR) and its indices depending on the status of body iron and the presence of infection in children, to evaluate their usefulness for recognizing the nature of anemia in infection, and to know the role of erythropoietic activity in these conditions.. Three hundred and sixty-eight children between 1 and 10 years were included: 206 healthy children; 60 iron deficient anemic children (IDA); 102 with anemia and infectious disease, 58 of them meeting criteria for IDA. We measured hemoglobin, red cell indices, reticulocytes, transferrin saturation, serum ferritin, erythrocyte protoporphyrin, serum erythropoietin, and sTfR. Statistic method: ANOVA test, multiple linear regression, and ROC curve.. sTfR, sTfR/ferritin ratio, and sTfR-logferritin index values were found to increase significantly in IDA children. These values were significantly lower in infectious anemia than iron deficiency states. Serum erythropoietin only was elevated significantly in iron deficiency states. In children without infection, mean corpuscular hemoglobin, erythrocyte protoporphirin, erythropoietin logarithm, and total-iron-binding-capacity logarithm predicted 81% of sTfR variability. sTfR and its indices showed a very high sensitivity and specificity for recognizing iron deficiency states. In children with IDA and infection sensitivity for sTfR/ferritin ratio was low (area under the curve: 0.71; 95% confidence interval: 0.64-0.88). For discriminating the nature of anemia in infection the cut-off point obtained for sTfR, sTfR/ferritin ratio, and sTfR-F index were 3, 70, and 1.8, respectively, and their sensitivity and specificity were also very high.. sTfR, sTfR/ferritin ratio, and sTfR-F index are useful parameters for recognizing iron deficiency and the nature of anemia in infection. In IDA+infection, sTfR/ferritin ratio should not be recommended in the diagnosis of iron deficiency. In iron deficiency, erythropoietic activity has a secondary role as predictor factor of sTfR levels.

Topics: Anemia, Iron-Deficiency; Biomarkers; Child; Child, Preschool; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Infant; Infections; Male; Protoporphyrins; Receptors, Transferrin; Reticulocyte Count; Transferrin

Partial correction of anemia by erythropoietin improves hemodialysis (HD)-associated immunosuppression. It is not known whether hemoglobin normalization improves immune status further. The authors prospectively compared the immune function of HD patients with congestive heart failure or ischemic heart disease on erythropoietin therapy randomized to normal versus anemic blood hemoglobin concentration. HD patients were randomized into a normal hemoglobin group (n = 17, target hemoglobin of 14 +/- 1 g/dl) or an anemic hemoglobin group (n = 18, target hemoglobin 10 +/- 1 g/dl). Delayed-type hypersensitivity, CD4 and CD8 counts, anti-tetanus toxoid antibody levels, erythrocyte complement receptor 1 expression, and lymphocyte proliferative responsiveness were measured. The observation period was 1 yr, and the trial was open label. Target hemoglobin was achieved and maintained in both groups. Significantly improved cutaneous reactivity was seen in the normal hemoglobin group (P = 0.003). The prevalence of anergy decreased in the normal hemoglobin group (from 60 to 20%) but increased in the anemic hemoglobin group (from 57 to 86%). The anemic hemoglobin group had higher CD8 counts compared with baseline (P = 0.0001) and compared with the normal hemoglobin group (P = 0.038). Both groups had significant increases in tetanus toxoid antibody levels after vaccination but without significant differences between groups. The anemic hemoglobin group had a progressive increase in erythrocyte complement receptor 1 levels compared with baseline (P = 0.002) and relative to the normal hemoglobin group (P = 0.023). There was no consistent pattern of altered proliferative responsiveness of lymphocytes. The data suggest that certain aspects of immune function, particularly delayed-type hypersensitivity, may be improved in HD patients by normalization of hemoglobin through the administration of increased doses of erythropoietin.

Topics: Aged; Anemia; Antibodies; CD4-CD8 Ratio; Cell Division; Erythrocytes; Erythropoietin; Female; Hemoglobins; Humans; Hypersensitivity, Delayed; Infections; Kidney Failure, Chronic; Lymphocytes; Male; Middle Aged; Prospective Studies; Receptors, Complement 3b; Recombinant Proteins; Renal Dialysis; Tetanus Toxin

Angiotensin-converting enzyme (ACE) inhibitors may exacerbate anemia in patients with chronic renal failure, as well as in dialysis patients. To better answer this question, a prospective, crossover study was conducted to evaluate the effect of ACE inhibitors on recombinant human erythropoietin (rHuEPO) requirements in hemodialysis patients. Patients administered an ACE inhibitor when entering the study remained on this drug for the initial 4 months and were then switched to another antihypertensive agent for 4 more months. Patients not initially administered an ACE inhibitor were switched to lisinopril at 4 months. rHuEPO doses were adjusted using a sliding scale based on weekly laboratory hematocrit values. The inclusion criteria were met by 51 patients undergoing dialysis. Demographics were as follows: 61% were women, 64% were black, 46% had diabetes, average age was 53.2 +/- 13.3 years, and time on hemodialysis was 38.0 +/- 44.5 months. Thirty-three patients completed the study. Hematocrit averaged 32.7% +/- 1.9% while on ACE inhibitor therapy and 33.1% +/- 2.1% off ACE inhibitor therapy (P = 0.217). There was no difference in rHuEPO dose per treatment during each period (3,500 +/- 1,549 U on ACE inhibitor therapy versus 3,312 +/- 1,492 U off ACE inhibitor therapy; P = 0.300). No significant differences were found in degree of blood pressure control or various clinical and laboratory parameters that might be associated with rHuEPO resistance between the two periods. Similarly, no differences were found in hospitalization days, duration of infections, or transfusion requirements. These findings suggest that ACE inhibitors do not contribute to rHuEPO resistance in hemodialysis patients.

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Blood Transfusion; Cross-Over Studies; Diabetes Complications; Drug Resistance; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hematocrit; Hospitalization; Humans; Infections; Kidney Failure, Chronic; Lisinopril; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors

To evaluate the therapeutic potential of hematopoietic growth factors (HGFs) during immunosuppressive treatment (IST) of severe aplastic anemia (SAA), 38 patients with newly diagnosed SAA received IST alone (group I), or IST plus recombinant human erythropoietin and granulocyte-macrophage colony-stimulating factor (rhEPO + rhGM-CSF) (group II). Eleven patients in each group received antilymphocyte globulin (ALG) for IST, and eight patients in each group received cyclosporine (CSA). Complete remission rates at one year were 26% and 74% for group I and group II patients, respectively. The ALG-treated subgroup showed the greatest differences between treatments. Compared with patients receiving ALG alone, patients treated with ALG plus HGFs had significantly better one-year survival (100% vs. 54.5%, P < 0.05), complete remission rates (91% vs. 36%, P < 0.05), more rapid and complete hematologic recovery, greater reductions in transfusion requirements, and lower infection rates. The data suggest a potential role for rhEPO + rhGM-CSF therapy in SAA patients receiving IST.

Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Blood Cell Count; Blood Transfusion; Bone Marrow Cells; Cell Count; Child; Drug Therapy, Combination; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Infections; Male; Middle Aged; Recombinant Proteins; Remission Induction; Survival Rate; Time Factors; Treatment Outcome

Topics: Adolescent; Anemia; Anemia, Iron-Deficiency; Biomarkers; C-Reactive Protein; Celiac Disease; Child; Erythropoietin; Female; Ferritins; Folic Acid; Hemoglobins; Hepcidins; Humans; Infections; Inflammatory Bowel Diseases; Iron; Male; Receptors, Transferrin; Transferrin; Vitamin B 12

Dendritic cells (DC) play a key role in the adaptive immune response due to their ability to present antigens and stimulate naïve T cells. Many bacteria and viruses can efficiently target DC, resulting in impairment of their immunostimulatory function or elimination. Hence, the DC compartment requires replenishment following infection to ensure continued operational readiness of the adaptive immune system. Here, we investigated the molecular and cellular mechanisms of inflammation-induced DC generation. We found that infection with viral and bacterial pathogens as well as Toll-like receptor 9 (TLR9) ligation with CpG-oligodeoxynucleotide (CpG-ODN) expanded an erythropoietin (EPO)-dependent TER119

Topics: Animals; Biomarkers; Blood Group Antigens; CD11c Antigen; Cell Differentiation; Cytokines; Dendritic Cells; Disease Models, Animal; Erythropoietin; Female; Hematopoiesis, Extramedullary; Immunity, Innate; Immunophenotyping; Infections; Inflammation; Mice; Mice, Transgenic; Oligodeoxyribonucleotides; Spleen

This article focuses on the use of rEpo, IVIG, and rG-CSF in the NICU. It discusses the most recent studies and the most definitive and clinically relevant evidence, rather than summarizing all published studies. The last section was written for NICU practice groups that choose to use any of these medications and are seeking a consistent approach for doing so. The section provides the author's approach to the use of rEpo, IVIG, and rG-CSF, revealing personal preferences, interpretations, and experiences, and is based on the dictum, "if you are going to use it, use it the same way each time."

Topics: Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Humans; Immunoglobulins, Intravenous; Infant, Newborn; Infant, Newborn, Diseases; Infections; Intensive Care Units, Neonatal; Neuroprotective Agents; Recombinant Proteins

The aim of this retrospective cohort study was to identify early risk factors of mortality and develop a mortality risk stratification instrument for severely anaemic Jehovah's Witness patients. It has been shown that Jehovah's Witness patients with the Auckland Anaemia Mortality Risk Score (Auckland AMRS) of 0 to 3 had 4% mortality, Auckland AMRS 4 to 5 32%, Auckland AMRS 6 to 7 50% and Auckland AMRS 8 and above 83%. It is concluded that the Auckland AMRS predicts mortality of severely anaemic Jehovah's Witness patients.

Topics: Adolescent; Adult; Aged; Anemia; Cardiovascular Diseases; Erythropoietin; Factor VIIa; Female; Filgrastim; Folic Acid; Granulocyte Colony-Stimulating Factor; Hemorrhage; Hospital Mortality; Hospitals, Public; Humans; Infections; Iron; Jehovah's Witnesses; Kidney Failure, Chronic; Male; Middle Aged; New Zealand; Plasma; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Risk Assessment; Risk Factors; Vitamin B 12; Young Adult

Although functional iron deficiency (FID) may be present in hemodialysis (HD) patients with high serum ferritin levels (>800 ng/mL), current protocols often preclude the use of intravenous (IV) iron in these patients. However, it has not been demonstrated that iron supplementation during erythropoietin therapy is ineffective or unsafe in increasing hemoglobin (Hb) levels in patients with high serum ferritin. This report describes the hematologic efficacy and safety of ferric gluconate (FG) therapy in patients with serum ferritin >800 ng/mL. A retrospective analysis was performed on HD patients at a single California dialysis center from January 1 to December 31, 2003. Patients classified as having high ferritin levels (serum ferritin >800 ng/mL on at least 66% of routine monthly measurements and transferrin saturation [TSAT] <25% on at least 1 occasion) were stratified as follows: patients in Group I were suspected of having FID and received FG > or =250 mg IV over a 3-month period when Hb was <11 g/dL, and patients in Group II were thought not to have FID and received <250 mg FG over a 3-month period. Both groups received standard recombinant human erythropoietin therapy as per the unit's protocol. Of 496 patients, 95 exhibited high ferritin and of these, 39 patients had sufficient data for analysis. Group I patients (n=14) showed a significant increase in Hb levels compared with Group II (n=25). There was no increase in ferritin levels in response to iron administration. No significant differences in hospitalizations or infections were observed between groups. Hemodialysis patients with high ferritin levels may have FID, and IV iron therapy safely improves FID in some patients. A larger randomized trial examining the optimal management of iron administration in HD patients with high ferritin levels is warranted.

Topics: Aged; Case-Control Studies; Drug Resistance; Erythropoietin; Female; Ferric Compounds; Ferritins; Hemoglobins; Hospitalization; Humans; Infections; Iron Deficiencies; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies

We previously showed that nutritional protein concentrations were predictive of outcome, whereas variables reflecting body composition and dialysis dose were not, in a 30-month prospective follow-up of 1,610 hemodialysis patients. Information on dialysis membrane and erythropoietin use had to be evaluated in an additional follow-up.. A subset of 650 patients from the initial cohort of 1,610 was analyzed for survival in a 2-year extension of follow-up. Detailed data were collected: demographics; cause of renal failure; time on dialysis therapy; type of membrane; erythropoietin treatment; body mass index (BMI); predialysis albumin, prealbumin, and bicarbonate levels; and outcome. Normalized protein catabolic rate (nPCR), dialysis adequacy, and lean body mass were computed from predialysis and postdialysis urea and creatinine values.. Patient characteristics were age of 61 +/- 16 years, 58% men, BMI of 22.7 +/- 4.4 kg/m2 , time on dialysis therapy of 102 +/- 73 months, and 8.8% had diabetes. Dialysis parameters were duration of 247 +/- 31 minutes, Kt/V of 1.4 +/- 0.3, and nPCR of 1.2 +/- 0.3 g/kg/d. Albumin level was 3.73 +/- 0.53 g/dL (37.3 +/- 5.3 g/L), and prealbumin level was 31 +/- 8 mg/dL. The survival rate was 78.7% after 2 years. Survival was influenced by age, presence of diabetes, use of high-flux membrane, and serum albumin level, but not other variables, including Kt/V and prealbumin level. Two-year variations in values for urea, creatinine, and weight were predictive of survival in univariate, but not multivariate, analyses.. In patients on dialysis therapy for a long period, better survival was observed when high-flux dialysis membranes were used.

Topics: Aged; Bicarbonates; Body Composition; Body Mass Index; Cardiovascular Diseases; Cause of Death; Cholesterol; Comorbidity; Creatinine; Diabetic Nephropathies; Erythropoietin; Female; Follow-Up Studies; Humans; Infections; Kidney Failure, Chronic; Life Tables; Male; Membranes, Artificial; Middle Aged; Neoplasms; Permeability; Prealbumin; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin; Survival Analysis; Time Factors; Urea

Topics: Anemia; Blood Substitutes; Emergency Medical Services; Erythrocyte Transfusion; Erythrocytes; Erythropoietin; Fluorocarbons; Hemorrhage; Humans; Infections; Recombinant Proteins; Resuscitation; Risk Factors

Arteriovenous fistulas are the recommended permanent vascular access (VA) for chronic hemodialysis. However, in the United States most patients begin chronic hemodialysis with a catheter. Recent data suggest that VA type contributes to recombinant human erythropoietin (rHuEPO) resistance. We examined catheter insertions, VA infections, and anemia management in Medicare, rHuEPO-treated, chronic hemodialysis patients.. We compared hemoglobin values and rHuEPO and intravenous iron dosing with concurrent catheter insertions and VA infections in 186,348 period-prevalent patients in 2000. We studied anemia management after catheter insertions and VA infections in 67,410 incident patients from 1997 to 1999. Multiple linear regression models examined follow-up hemoglobin and rHuEPO dose per week (rHuEPO/wk) by numbers of catheter insertions and hospitalizations for VA infection.. In the prevalent cohort, increasing temporary and permanent catheter insertions and VA infections were associated with slightly lower hemoglobin, higher rHuEPO doses, and higher intravenous iron doses. In the incident cohort, compared to patients with no VA infections or no catheter insertions (temporary or permanent), respectively, patients with 2+ VA infections or 2+ catheter insertions had 0.12 g/dL and 0.06 g/dL lower mean hemoglobin (P = 0.0028 and P < 0.0001), and 25.7% and 12.2% higher mean rHuEPO/wk (P < 0.0001).. Higher rHuEPO doses may be required to maintain similar or slightly lower mean hemoglobin values among chronic hemodialysis patients with higher numbers of catheter insertions and VA infections, compared to patients without any.

Topics: Adolescent; Adult; Aged; Anemia; Arteriovenous Shunt, Surgical; Child; Child, Preschool; Cohort Studies; Erythropoietin; Female; Hemoglobins; Humans; Incidence; Infant; Infant, Newborn; Infections; Kidney Failure, Chronic; Male; Middle Aged; Prevalence; Recombinant Proteins; Renal Dialysis; Urinary Catheterization

Topics: Anemia; Anemia, Iron-Deficiency; Erythropoietin; Female; Humans; Immunosuppressive Agents; Infections; Kidney Transplantation; Liver Failure; Male; Postoperative Complications; Retrospective Studies; Sex Characteristics

Topics: Aged; Anemia; Arteriovenous Shunt, Surgical; Cardiovascular Diseases; Catheterization, Central Venous; Comorbidity; Erythropoietin; Female; Hematocrit; Hemoglobins; Hospitalization; Humans; Infections; Kidney Failure, Chronic; Male; Middle Aged; Practice Guidelines as Topic; Renal Dialysis

This study analyses the factors affecting mobilisation and engraftment in autologous peripheral blood progenitor cell transplantation according to the number of CD34(+) re-infused.. A total of 190 patients underwent mobilisation with G-CSF alone (n=113) or in combination with chemotherapy (n=77). A total of 116 patients (61%) were autografted with <2 x 10(6) CD34(+) cells/kg and 74 patients were transplanted with >2 x 10(6) CD34(+) cells/kg. Rates of granulocyte and platelet recovery were estimated using the product-limit method of Kaplan-Meier and compared using a log-rank test. The Cox regression model was used for the multivariate analysis of factors influencing engraftment. Differences between cohorts were evaluated by one-way ANOVA or Mann-Whitney tests, and multivariate analysis was performed using a stepwise lineal regression.. Neutrophil and platelet engraftment was significantly longer with <2 x 10(6)/CD34(+)/kg (12 vs 10 days, P=0.014 and 16 vs 13 days, P=0.0001 respectively). Platelet recovery was affected by exposure to alkylating agents (P=0.04), refractory disease (P=0.02) and AML (P=0.0001), but only the last two variables remained significant in Cox regression (P<0.01). Granulocyte engraftment was longer in CML (univariate, P=0.04) and in refractory disease (multivariate, P=0.02). In patients re-infused with >2 x 10(6)/CD34(+)/kg, the Cox model did not identify prognostic factors for haematopoietic recovery.. Although mobilisation schedules and disease status influenced not only the yield of progenitor cells, but also the engraftment kinetics, the number of CD34(+) re-infused was the main predictor of haematopoietic recovery. While engraftment succeeded in most of the cases, the re-infusion of >2 x 10(6)/CD34(+)/kg resulted in significantly shorter recovery times.

Topics: Adolescent; Adult; Aged; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Caspase 14; Caspases; Cerebral Hemorrhage; Cohort Studies; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Erythropoietin; Etoposide; Female; Graft Survival; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Hydroxyurea; Infections; Leukapheresis; Life Tables; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Transplantation Conditioning; Transplantation, Autologous

In 1980, the first Moroccan hemodialysis center was founded in Casablanca. The number of centers has been increasing since then, to reach 61 centers to wards the of 1996. There are 1800 hemodialysed (males 59%, females 41%) with and average age of 51 +/- 4 years. In about one third of the cases, the cause of the end stage renal failure remains unknown. However, chronic glomerulonephritis comes at the head of known causes (25%), followed by interstitial nephritis (19%). A temporary vascular access (catheter) was necessary in 81% of cases when dialysis has started in emergency in 61% of patients. Infections were the most frequent complications (21%) namely septicaemia (8%) and tuberculosis (7%). The vaccination against hepatitis B virus is done systematically in all the centers, and the number of chronic carriers of HBS Ag is about 7%. Further more, serological C virus is positive in 40% of the hemodialysed patients. Cardio-vascular complications were dominated by percarditis (13%) especially at the beginning of the dialysis. Anaemia remains very frequent and often very important requiring multiple blood transfusions (35%) in the absence of erythropoietin treatment. The death rate, which is very difficult to estimate, is of about 18%. Peritoneal dialysis was used in 50 patients but only four patient continued on peritoneal dialysis therapy. 108 patients were transplanted (23 cases in Morocco, 85 in other countries) with a waiting list of 0 to 12 years. Hemodialysed Moroccan's population is characterised by the high number of unknown causes and the gravity of the admission stage. A renal effort in prophylactic should be performed to avoid certain causes of renal failure.

Topics: Adolescent; Adult; Aged; Ambulatory Care Facilities; Anemia; Cardiovascular Diseases; Carrier State; Catheters, Indwelling; Child; Child, Preschool; Comorbidity; Erythropoietin; Female; Glomerulonephritis; Hepatitis, Viral, Human; Humans; Infant; Infections; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Morocco; Nephritis, Interstitial; Peritoneal Dialysis; Renal Dialysis; Transfusion Reaction; Vaccination

According to an unreliable meta-analysis, epoetin beta reduces the number of premature neonates needing transfusions for anaemia by 18% on average. When such children do require transfusions, two comparative trials have shown a reduction in the frequency of transfusions and total volume of blood transfused, but the clinical consequences were not studied. Thus clinical experience to date is too limited to rule out a risk of possibly severe adverse events. Furthermore, prescription of epoetin beta must be accompanied by iron supplementation, whose optimal dose and route of administration have not been established. The cost-benefit ratio of epoetin beta in the prevention of anaemia in premature infants must be thoroughly assessed in the context of national health systems.

Topics: Anemia, Neonatal; Blood Transfusion; Clinical Trials as Topic; Cost-Benefit Analysis; Erythropoietin; France; Humans; Infant, Newborn; Infant, Premature; Infections; Iron Deficiencies; Iron, Dietary; Meta-Analysis as Topic; Treatment Outcome

Topics: Acquired Immunodeficiency Syndrome; Anemia; Drug Resistance; Erythropoietin; Humans; Infections; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins

Ten continuous ambulatory peritoneal dialysis (CAPD) patients experienced 23 episodes of peritonitis and were treated with intraperitoneal (IP) antibiotics as per sensitivity report. Serum ferritin was measured before and after the treatment. In 6 patients, erythropoietin (EPO) was also measured before and after the treatment. There was a significant drop in the serum EPO levels after therapy compared to the levels before, whereas serum ferritin levels did not change.

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Erythropoietin; Female; Ferritins; Hematocrit; Hemoglobins; Humans; Infant; Infections; Kidney Failure, Chronic; Male; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis

Infection and inflammation are common problems in patients with end-stage renal disease. Both conditions can interfere with normal erythropoiesis and lead to a worsening of anemia and a suboptimal response to Epoetin alfa therapy. By understanding the pathophysiologic effects of infection and inflammation, assessing the patient's clinical status, and analyzing relevant laboratory values, nurses can intervene early and minimize the impact of these conditions on hematocrit.

Topics: Adult; Anemia; Diagnosis, Differential; Erythropoietin; Humans; Infections; Inflammation; Kidney Failure, Chronic

Nowadays, maintenance dialysis can be proposed to patients suffering from myeloma with end-stage chronic renal failure. We report here data from eight patients dialysed either by hemo- (6) or peritoneal dialysis (2), together with chemotherapy in half of them. Six patients died; the longest survival has been about 6 years. The main cause of morbidity was sepsis, especially in peritoneal dialysis patients; therefore we now favour hemodialysis in patients exposed to aggressive chemotherapy. We think dialysis justified in all cases, including those with high tumor mass, in order to expect the effect of chemotherapy; then, provided good response to drugs, further survival can be consistently improved. Once on maintenance dialysis, main drawbacks for these patients are cardiovascular complications (AL amyloidosis) and above all anemia; the latter however can be markedly improved, thanks to erythropoietin therapy which provides these patients with much better quality of life.

Topics: Aged; Aged, 80 and over; Erythropoietin; Female; Humans; Infections; Kidney Failure, Chronic; Male; Middle Aged; Multiple Myeloma; Peritoneal Dialysis; Prognosis; Renal Dialysis; Retrospective Studies

To analyze the relationship between serum erythropoietin levels and hemoglobin levels in elderly patients with anemia of chronic disorders related to cancer or acute infection when compared with anemic patients with iron deficiency.. Prospective survey with comparison groups.. Tertiary care center.. An elderly group aged 70 and above (mean 84, range 70-96) was divided into subgroups of 45 with anemia of chronic disorders (23 with cancer and 22 with acute infection), 24 with iron-deficiency anemia, and 27 with no anemia. Thirty non-anemic younger adults were also studied.. Serum erythropoietin (radioimmunoassay), complete blood count, serum iron, B12, folate and ferritin, liver and kidney function tests, blood gas analyses, and bacteriological and radiological tests.. The serum erythropoietin levels were significantly lower in the elderly non-anemic hospitalized group than in the healthy younger group. A significant negative relationship between the log serum erythropoietin and hemoglobin levels was found in patients with iron deficiency, but not in the other groups. For any given hemoglobin level, the response of erythropoietin was significantly higher in anemic patients with iron deficiency when compared with the neoplastic and infectious group.. Erythropoietin response to anemia is blunted in elderly patients with anemia of chronic disorders related to cancer or acute infection. Erythropoietin level is lower in non-anemic elderly inpatients than in healthy younger persons.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anemia; Anemia, Hypochromic; Case-Control Studies; Chronic Disease; Erythropoietin; Female; Hemoglobins; Hospitalization; Humans; Infections; Male; Neoplasms; Prospective Studies

Staphylococcus aureus nasal carriage status (SANCS) has been recognized as a risk factor for patients on CAPD, due to a higher probability of suffering peritoneal catheter infections. The use of subcutaneous drugs (insulin dependent diabetics, drug addicts, HD patients and antiallergic vaccines), has been associated with increased risk of SANCS. On CAPD, erythropoietin (EPO) is almost universally used by the subcutaneous route. The objective of this paper was to evaluate the incidence and prevalence of SANCS in 85 CAPD patients by means of nasal smear and the influence of SANCS on peritoneal and catheter infection rate. Patients were divided in four groups according to diabetic status and EPO treatment (mean dose 2000 u. twice a week). The prevalence of SANCS in control groups was 30% in non-diabetics and 23% in diabetics. EPO treated patients showed a prevalence of SANCS of 39% in non-diabetics and 45% in diabetics due to the presence of 7 and 5 carrier patients respectively. SANCS patients (29% of the population), suffered 45% of peritonitis and 42% of exit-site infections caused by S. aureus. In a prospective part of the study, there was no difference in the frequency of developing positive cultures among EPO and control (30% of patients). No male EPO treated patients developed SANCS. We conclude that it is necessary to monitor S. aureus nasal carrier status periodically in CAPD patients especially in women. Whether or not subcutaneous erythropoietin treatment is implicated pathogenetically with SANCS, is not clarified by our data because of the frequent spontaneous appearance of SANCS among CAPD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cross-Sectional Studies; Erythropoietin; Female; Humans; Infections; Male; Middle Aged; Nasal Cavity; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prospective Studies; Recombinant Proteins; Retrospective Studies; Risk Factors; Staphylococcus aureus

Response to Epoetin alfa can be influenced by several factors, including the presence of inflammation or infection. It is important that nurses monitor patients so that possible undesirable effects of inflammation or infection can be avoided or minimized.

Topics: Adult; Anemia; Erythropoietin; Female; Humans; Infections; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Patient Care Planning

Topics: Adult; Anemia; Erythrocyte Aging; Erythropoietin; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infections; Male; Recombinant Proteins

Topics: Adult; Aged; Anemia; Colony-Stimulating Factors; Endocrine System Diseases; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Humans; Infections; Liver Diseases; Male; Neoplasms; Rheumatic Diseases

Topics: Adult; Aluminum; Anemia; Anemia, Hypochromic; Erythropoiesis; Erythropoietin; Humans; Hyperparathyroidism; Infections; Iron Deficiencies; Kidney Failure, Chronic; Middle Aged; Occult Blood; Recombinant Proteins; Renal Dialysis

Topics: Abscess; Anemia; Dose-Response Relationship, Drug; Drug Resistance; Erythropoietin; Female; Humans; Infections; Kidney Failure, Chronic; Middle Aged; Recombinant Proteins; Renal Dialysis

Nursing management of anemic dialysis patients requires a thorough understanding of the conditions that can potentially affect erythropoiesis. Erythropoietin deficiency has been documented as the primary cause of the anemia of uremia, and Epoetin alfa has proven to be an effective therapy for correcting this condition. However, other etiologies, independent of the uremic process, can also contribute to anemia in these patients and lead to a diminished response to Epoetin alfa. Iron deficiency and blood loss, for example, are well-documented etiologies that can hinder erythropoiesis and diminish the response to Epoetin alfa (Van Wyck, 1989). Another etiology still under investigation is the potential effect of infection or inflammation on the response to Epoetin alfa. This article examines the anemia of infection and inflammation and the potential effect on response to Epoetin alfa.

Topics: Adult; Anemia; Erythropoietin; Female; Humans; Infections; Kidney Failure, Chronic; Male; Middle Aged

18 anemic patients undergoing maintenance hemodialysis were treated with recombinant human erythropoietin (EPO) 1-3 times per week for 10.7 +/- 3 months. 4 patients underwent renal transplantation whereas 14 patients could be followed up during 12 months of EPO treatment. Hemoglobin concentration rose (from 7.0 +/- 0.7 to 11.0 +/- 1.1 g/dl, p less than 0.001) with an EPO maintenance dose of 298 units/kg/week. Blood transfusions were totally eliminated. 12 patients without iron overload required iron supplements. In the course of an infectious episode and notwithstanding an increase in EPO dosage, 2 patients exhibited a fall in hemoglobin which rose again after successful treatment of the infection. The few complications observed in connection with the rise in hemoglobin were: 1. deterioration of arterial hypertension in 7/18 with hypertensive encephalopathy in 3 patients, 2. thrombotic occlusion of the vascular hemodialysis access (a-v fistula) in 3/18, 3. periarticular inflammation with calcified deposits due to an elevated calcium-phosphorus product of 6.8 mmol/l in 4/18, 4. occurrence of hyperkalemia (6.9 +/- 0.3 mmol/l) in 7/18. These complications were more frequent during the first 3 months. They were corrected with close monitoring, drug therapy for hypertension, and intensification of dialysis and of treatment with phosphate binding substances, with the result that no differences were found in 14 patients before and after 12 months of treatment with EPO (blood pressure 133 +/- 25/77 +/- 9 vs 139 +/- 26/79 +/- 13 mm Hg [ns], potassium 5.4 +/- 0.4 vs 5.6 +/- 1.0 mmol/l [ns] and calcium-phosphorus product 4.3 +/- 1.0 vs 4.6 +/- 1.3 [ns]).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Anemia, Hypochromic; Calcium; Erythropoietin; Female; Hemoglobins; Humans; Hyperkalemia; Hypertension; Infections; Male; Middle Aged; Phosphorus; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Autoantibodies; Chronic Disease; Erythropoietin; Hemolysis; Humans; Infections; Iron; Neoplasms

Erythropoietin responsible for the hormonal regulation of red blood cell production. Its formation is largely controlled by the kidneys. A number of assay methods for erythropoietin are available. Asymptomatic patients with sickle cell disease have elevated erythropoietin levels, as expected with chronic hemolysis. When complicated by chronic renal failure, erythropoietin levels do not rise appropriately. Chronic infection has not been studied, but the erythropoietin response in acute infection does not seem to conform to a pattern. Aplastic crises are characterized by very high levels of erythropoietin, suggesting bone marrow suppression, but events that trigger the crises remain obscure. In vaso-occlusive crises, there is also some suggestion of mild and transient lack of bone marrow response. Patients with sickle cell disease, with their chronic high erythropoietin anemia and susceptibility to altered states, are uniquely suited for investigating the physiology of erythropoietin, especially under the constraints of present assay methods.

Topics: Anemia, Sickle Cell; Erythropoietin; Hematopoietic Stem Cells; Humans; Infections; Kidney; Kidney Failure, Chronic

Erythropoiesis was evaluated in 37 patients with sickle cell anaemia, 26 of them children under 12 years of age. Mean haemoglobin, haematocrit, reticulocyte, and erythropoietin levels were similar for 11 who were asymptomatic, 11 with infections, and 12 in vaso-occlusive crisis. Mean haemoglobin, haematocrit, and reticulocyte values were significantly lower and the mean erythropoietin level significantly higher for three patients in aplastic crisis. Reticulocyte counts reflected erythropoietic activity during the asymptomatic state but were variable during infection and crisis. No erythropoietic inhibitory activity was found in any of the four clinical states. It has been suggested that erythropoietin production decreases during infection. Patients in this study responded appropriately to stress, showing no decrease in erythropoietic activity during acute infection or crisis.

Topics: Adolescent; Adult; Anemia, Sickle Cell; Blood Cell Count; Child; Child, Preschool; Erythropoiesis; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Infant; Infections; Male; Reticulocytes; Thrombosis; Vascular Diseases

A major factor in the anemia of infection, inflammation, and malignancy is a relative failure of the bone marrow to increase erythropoiesis in response to a shortened red cell survival. The possible causes for this diminished marrow response are: (a) a reduced production of erythropoietin, or, (b) impaired bone marrow response to erythropoietin. In this report studies were performed on 6 normals, 13 patients with anemia from infection or inflammation, and 18 patients with anemia caused by advanced malignancy. Serum erythropoietin activity was measured using the posthypoxic, polycythemic mouse assay. Assessment of bone marrow response to erythropoietin was made by measuring (59)Fe-heme synthesis in bone marrow suspensions cultured for 3 days with and without the addition of erythropoietin. The results showed that marrow heme synthesis was increased in erythropoietin-treated cultures as compared with saline control cultures by 66+/-8% (mean +/-SE) in normals, 101+/-10% in patients with infection or inflammation, and 31+/-5% in malignancy. Serum erythropoietin levels were consistently diminished relative to expected levels for the degree of anemia in the infection-inflammatory group, but not in malignancy. In these patients, plasma inhibitors to the biological activity of erythropoietin were not detected in vitro. These studies suggest that another factor to consider in the anemia of malignancy is a decreased bone marrow response to erythropoietin. In the anemia of infection-inflammation, marrow response to erythropoietin is normal, but serum levels of erythropoietin are decreased relative to the degree of anemia.

Topics: Aged; Anemia; Animals; Arthritis, Rheumatoid; Biological Assay; Bone Marrow; Bone Marrow Cells; Cells, Cultured; Dose-Response Relationship, Drug; Erythropoiesis; Erythropoietin; Female; Heme; Humans; Infections; Iron Radioisotopes; Male; Mice; Middle Aged; Neoplasms; Rats

Topics: Anemia; Child, Preschool; Erythrocytes; Erythropoiesis; Erythropoietin; Gastrointestinal Diseases; Humans; Infant; Infections; Lymphocyte Culture Test, Mixed

Topics: Animals; Bone Marrow Cells; Busulfan; Cell Division; Clone Cells; Endotoxins; Erythrocytes; Erythropoietin; Female; Femur; Hematopoietic Stem Cells; Hypoxia; Infections; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Organ Size; Polycythemia; Radiation Chimera; Rauscher Virus; Spleen; Virus Replication

Topics: Anemia; Arthritis, Rheumatoid; Blood Proteins; Bone Marrow; Bone Marrow Cells; Chronic Disease; Erythropoietin; gamma-Globulins; Hematocrit; Humans; Infections; Iron; Neoplasms; Protein Biosynthesis; Serum Albumin; Transferrin; Vitamin B 12

The serum level of erythropoietin was measured in 31 patients with anemia secondary to chronic infection or malignancy and compared with erythropoietin levels in 23 patients with iron-deficiency anemia and 14 patients with primary hematopoietic diseases. Erythropoietin levels varied directly with the degree of anemia in patients with iron deficiency or primary hematopoietic disorders. There was no correlation of erythropoietin and the degree of anemia in patients with chronic infection or malignancy and the erythropoietin levels were significantly lower than in patients with iron deficiency or primary hematopoietic disease and the same degree of anemia. A major factor in the anemia of chronic disorders is a decrease in levels of erythropoietin.

Topics: Anemia; Anemia, Hypochromic; Animals; Biological Assay; Bone Marrow Diseases; Carcinoma; Chronic Disease; Erythropoietin; Hodgkin Disease; Humans; Infections; Lymphoma, Non-Hodgkin; Male; Mice; Middle Aged; Neoplasms; Neutralization Tests