Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth factors or humoral agents can support haemopoiesis in various bone marrow disorders. They have the ability to act on multiple cell lineages and in myeloid cells, and the potential to act on the neoplastic equivalent of normal cells. Anaemia is a common feature of multiple myeloma seen in at least two-thirds of patients at presentation. Erythropoietin is increasingly being used with variable effect for the treatment of this anaemia, especially in cases associated with renal failure and in patients in whom blood transfusion may be undesirable or contraindicated. We describe a patient treated with recombinant erythropoietin who developed fulminating malignant transformation. The demonstration of erythropoietin receptors on a human myeloma cell line and the occurrence of the rare complication of plasma cell leukaemia in our patient stresses the need for caution and invites detailed clinical and laboratory studies before its general use.
 ...
PMID:Does erythropoietin accelerate malignant transformation in multiple myeloma? 913 33

Human recombinant erythropoietin is used to treat chronic anemia in patients with end-stage renal failure. Erythropoietin causes hypertension, and hypertensive encephalopathy has been associated with its use. We describe six dialysis-dependent, chronic renal failure patients who developed hypertension, headache, and seizures while on erythropoietin. Four of the six patients had posterior white matter changes on neuroimaging. The encephalopathy was managed by prompt antihypertensive and anticonvulsant treatment and by discontinuation of erythropoietin. Hypertensive posterior leukoencephalopathy is associated with erythropoietin use.
 ...
PMID:Erythropoietin-associated hypertensive posterior leukoencephalopathy. 971 75

Absolute and functional iron deficiency is the most common cause of epoetin (recombinant human erythropoietin) hyporesponsiveness in renal failure patients. Diagnostic procedures for determining iron deficiency include measurement of serum iron levels, serum ferritin levels, saturation of transferrin and percentage of hypochromic red blood cells. Patients with iron deficiency should receive supplemental iron, either orally or intravenously. Adequate intravenous iron supplementation allows reduction of epoetin dosage by approximately 40%. Intravenous iron supplementation is recommended for all patients undergoing haemodialysis and for pre-dialysis and peritoneal dialysis patients with severe iron deficiency. During the maintenance phase (period of epoetin therapy after correction of iron deficiency), the use of low-dose intravenous iron supplementation (10 to 20 mg per haemodialysis treatment or 100 mg every second week) avoids iron overtreatment and minimises potential adverse effects. Depending on the degree of pre-existing iron deficiency, markedly higher iron doses are necessary during the correction phase (period of epoetin therapy after correction of iron deficiency) [e.g. intravenous iron 40 to 100 mg per haemodialysis session up to a total dose of 1000 mg]. The iron status should be monitored monthly during the correction phase and every 3 months during the maintenance phase to avoid overtreatment with intravenous iron.
 ...
PMID:Safety aspects of parenteral iron in patients with end-stage renal disease. 935 60

Recombinant human erythropoietin is used in clinical practice mainly for treatment of anemia of renal failure. In the past years, however, its use has been approved for other indications, including prevention of anemia in surgical patients or in patients undergoing platinum-based chemotherapy, treatment of anemia of prematurity, of anemia induced by zidovudine therapy in HIV-infected patients, and of anemia induced by chemotherapy of nonmyeloid malignancies. Erythropoietin should routinely be given subcutaneously to maximize its effects. Most patients undergoing rHuEpo treatment develop functional iron deficiency, a situation in which iron supply to the erythroid marrow is inadequate for the erythrocyte precursor demand. Iron supplementation should, therefore, be given to all individuals receiving rHuEpo except for those patients with increased serum iron and transferrin saturation. Outside the setting of uremia, only a portion of patients can clearly benefit from erythropoietin therapy; therefore, the use of rHuEpo should be individualized in nonrenal applications.
 ...
PMID:How and when to use erythropoietin. 957 Jul 2

First used successfully to correct the anemia associated with chronic renal failure, epoetin alfa has been shown to be highly effective in many patients with either hematologic or nonhematologic malignancies. Multiple studies have demonstrated effective response rates, with increases in hemoglobin concentration and reduction or elimination of transfusion requirements in up to 75% or 80% in such patients. Nevertheless, as clinical experience has grown, several issues have arisen. First, not all cancer patients respond to epoetin alfa and, consequently, it is important to identify those patients most likely to respond to make early clinical decisions regarding dose adjustment or drug withdrawal. Second, experience in patients with renal failure has revealed a state of "functional iron deficiency" and, thus, highlighted the importance of iron supplementation to optimize the response to epoetin alfa. Does "functional iron deficiency" complicate epoetin alfa therapy of patients with the anemia of cancer, and could such patients benefit from iron supplementation? Finally, some hematologic malignancies, especially myelodysplastic syndromes, can be resistant to epoetin alfa monotherapy. Can the effective response rates in such patients be improved by combining epoetin alfa therapy with the administration of other hematopoietic growth factors? Epoetin alfa has made substantial contributions to the care of patients with cancer and, with time, additional uses for this very valuable drug will become apparent.
 ...
PMID:Epoetin alfa: into the new millennium. 967 36

Erythropoietin (EPO) is the glycoprotein hormone that promotes differentiation of erythroid progenitor cells in bone marrow. The normal kidney produces EPO to maintain erythrocyte for oxygen supply. This hormone activity was found in the serum of anemic animals in the 1890s. Renal failure results in severe anemia because of reduced EPO production, therefore anemia patients expected EPO treatment for long time. However, this was difficult due to the limited amount of EPO. Many researchers have tried to isolate EPO since the 1950s. Finally Miyake and Goldwasser purified highly active EPO from the urine of aplastic anemia patients. Since then, the characteristics and structural information from the purified material accelerated the cloning of the EPO gene. Mammalian cells were essential to produce EPO, because EPO contains 40% carbohydrate that plays some important roles in its activity, stability and biosynthesis. In 1984, two groups succeeded in cloning the EPO gene and expressing this gene in mammalian cells. Recombinant human EPO is currently available for anemia treatment. In this paper, we review production in mammalian cells, molecular characterization, especially carbohydrate moieties, and clinical applications of recombinant EPO.
 ...
PMID:The production of recombinant human erythropoietin. 970 92

Erythropoietin (Epo) controls the proliferation, differentiation and survival of the erythroid progenitors. This cytokine was cloned in 1985 and rapidly became used for treatment of anemia of renal failure, opening the way to the first clinical trials of a hematopoietic growth factor. The clonage of one chain of the Epo receptor followed in 1989, thereby opening the research on intracellular signal transduction induced by Epo. Epo is synthesized mainly by the kidney and the liver and sequences required for tissue-specific expression have been localized in the Epo gene. A 3'enhancer is responsible for hypoxia-inducible Epo gene expression. HIF-1 alpha and beta proteins bind to this enhancer. Gene regulation by hypoxia is widespread in many cells and involves numerous genes in addition to the Epo gene. The Epo receptor belongs to the cytokine receptor family and includes a p66 chain which is dimerized upon Epo activation; two accessory proteins defined by cross-linking remain to be characterized. Epo binding induces the stimulation of Jak2 tyrosine kinase. Jak2 activation leads to the tyrosine phosphorylation of several proteins including the Epo receptor itself. As a result, different intracellular pathways are activated: Ras/MAP kinase, phosphatidylinositol 3-kinase and STAT transcription factors. However, the exact mechanisms by which the proliferation and/or the differentiation of erythroid cells are regulated after Epo stimulation are not known. Furthermore, target disruption of both Epo and Epo receptor showed that Epo was not involved in the commitment of the erythroid lineage and seemed to act mainly as a survival factor.
 ...
PMID:Biology of erythropoietin. 979 57

Many patients with solid tumours or haematological malignancies develop anaemia, and the use of chemotherapy aggravates this condition. Red blood cell transfusions are often necessary but are associated with many risks, including immunosuppressive effects that may increase the risk of tumour recurrence. Many clinical studies have shown that epoetin (recombinant human erythropoietin) therapy can ameliorate, or even prevent, the anaemia associated with chemotherapy and cancer (including solid tumours as well as multiple myeloma or lymphoma). Response, defined as a significant (>50%) reduction in the rate of transfusions and/or a significant (>2 g/dl) elevation of haemoglobin levels, is usually observed in about 60% of the patients, irrespective of the type of standard chemotherapy given. The decrease in transfusion requirements is the major objective of epoetin therapy, because they are costly, inconvenient and are associated with potential adverse effects. Epoetin therapy also brings about substantial improvements in various indices of quality of life that are proportional to changes in haemoglobin level. However, large dosages of epoetin are generally required and about 40% of patients do not respond even to very high dosages. A number of adverse effects of epoetin therapy have been observed in patients with renal failure. The most prominent include hypertension, headaches, seizures and thrombotic events. These complications can also occur in patients with renal failure who are not receiving epoetin. Their exact incidence has been assessed in placebo-controlled studies, which have demonstrated that there is no increased risk of thrombosis or seizure with epoetin. However, it is now generally accepted that 10 to 20% of haemodialysis patients will experience an elevation of blood pressure because of epoetin and there is no doubt that a rapid elevation of blood pressure may cause generalised seizures. In other settings, including anaemia associated with cancer, very few adverse effects have been attributed to epoetin. However, close monitoring of blood pressure should be implemented in patients with hypertension. There is no evidence that epoetin stimulates tumour growth. With the dosages of epoetin currently used, there is no evidence of stem cell competition, resulting in thrombocytopenia or neutropenia, or of stem cell exhaustion, producing secondary anaemia when treatment is stopped. Epoetin is a remarkably well tolerated drug that offers significant benefits in patients with cancer.
 ...
PMID:A risk-benefit assessment of epoetin in the management of anaemia associated with cancer. 980 42

Erythropoietin (EPO) is a glycoprotein hormone produced principally by the kidney and is the major stimulus for erythropoiesis. Recombinant human EPO has now been biosynthesized and is available for clinical use, particularly in patients with renal failure. EPO has been reported to be effective in treating anaemia due to chronic renal failure. It has been used in pregnancy to correct anaemia following renal transplantation with graft dysfunction. We report here the case of a post-renal transplant patient who became pregnant and developed severe anaemia which was not related to iron, B12, or folate deficiency. Her anaemia was successfully treated with EPO with no evidence of rejection or significant graft dysfunction following therapy. She tolerated EPO very well, and there was a successful outcome of the pregnancy. This case has encouraged us to conclude that EPO has a useful role in the treatment of anaemia in pregnant women following renal transplantation.
 ...
PMID:Erythropoietin therapy in a pregnant post-renal transplant patient. 988 25

The target organ failures associated with uremia are most often considered to be caused by processes other than uremia per se. Heart disease, for example, is considered the product of hypertension, lipid abnormalities, and so forth, rather then the uremic state. Erythropoietin deficiency, blood loss, and iron deficiency are believed to cause anemia, rather than the uremic state. Malnutrition is believed to be the product of poor nutrient intake and perhaps nutrient losses, rather than uremia per se. This article reviews evidence suggesting that anemia and malnutrition share a common cause; the acute-phase inflammatory process that is a normal host-defense mechanism. Given the high prevalence of heart disease among patients with end-stage renal disease (ESRD), data indicating activation of the acute-phase process in patients with kidney failure, and emerging evidence that the process has a significant role in the risk for cardiovascular disease among patients without kidney failure, there is a strong likelihood that heart disease will share with anemia and malnutrition the acute-phase state as a contributing cause. Thus, instead of disconnected target organ failures, each with different antecedent causes, we see emerging the likelihood of a unifying pathobiology for uremia. The antecedents of morbidity and mortality appear as a web of organ failures connected by a common pathobiology. Whereas each failure likely has contributing causes other than the acute-phase state, they probably share the state as a causative, contributing, or exacerbating factor.
 ...
PMID:Acute-phase inflammatory process contributes to malnutrition, anemia, and possibly other abnormalities in dialysis patients. 989 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>