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

ESF deficiency is probably not a major contributing factor in the early stages of the anemia of renal insufficiency. Serum ESF titers are lower in advanced renal failure when compared to that of nonuremic anemic subjects suffering from equivalent anemia. With increasing renal insufficiency a relative ESF deficiency gains increasing importance as a pathogenic factor in reduced erythropoiesis. Kidneys without excretory function may still be erythropoietically effective, since a further increase in the anemia occurs after bilateral nephrectomy. However, a basal erythropoiesis is still maintained by extrarenal ESF production, which is also enhanced by hypoxia. ESF deficiency is compensated after successful renal transplantation. A decreased response of the bone marrow to ESF may be another factor contributing to the hypoproliferative state of erythropoiesis in uremia. As demonstrated in a chronic uremic rabbit model there may be a blockade of further differentiation of the erythroid precursors. The relationship of this blockade in differentiation to the inhibitor of heme synthesis is not clear.
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PMID:Role of erythropoietin in the anemia of renal insufficiency in man and in an experimental uremic rabbit model. 71 Jan 40

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.
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PMID:Diagnosis and treatment of pure red cell aplasia. 78 16

The effect of acute and chronic renal failure on cell proliferation in rapidly dividing tissues has been examined in man and animal models. The evidence reviewed supports the hypothesis that renal failure results in a general inhibition of cell proliferation. Cell population kinetic studies of gastrointestinal and skin epithelia in experimental acute renal failure show a prolongation of the cell generation cycle. Less detailed investigations of other proliferative cell systems indicate an inhibitory effect on proliferation within the generative compartment of the erythroid series, lymphoid tissue, seminiferous epithelia and wound granulation tissue. This inhibition appears partly responsible for anaemia and impaired wound healing and may contribute to the abnormal immune responses, gastrointestinal tract lesions and male sterility found in renal failure.
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PMID:Inhibition of cell proliferation in renal failure and its significance to the uraemic syndrome: a review. 122 2

The erythropoietic response to graded doses of recombinant human erythropoietin (epoetin alfa) was assessed in 24 hemodialysis patients by quantitative ferrokinetic studies, and measurement of the reticulocyte count and plasma levels of transferrin receptor protein. These responses were compared to those of 22 normal subjects. Epoetin alfa was given intravenously at 15, 50 or 150 U/kg every other day for four injections. Three patients with chronic renal failure were restudied after renal function was restored following renal transplantation. The results of these three different measurements of erythroid function showed that the acute response to recombinant human erythropoietin was similar in normal subjects and patients with renal failure. We conclude that chronic uremia does not alter the responsiveness to erythropoietin in vivo.
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PMID:A comparison of the responses to recombinant human erythropoietin in normal and uremic subjects. 140 23

Recombinant human erythropoietin (rHuEpo) is now widely employed in correction of the anemia of end stage renal disease (ESRD). Recent reports suggest that rHUEpo, in addition to its effect on CFU-E and burst-forming-unit-erythroid (BFU-E), may stimulate granulocyte/macro-phage production and pluripotential progenitors of the myeloid and monocyte lineage. Furthermore, there is now data which demonstrate that ESRD patients who received rHuEpo have enhanced cytokine production. Taken together, these observations suggest that the administration of rHuEpo may augment the diminished immune response of renal failure patients. To evaluate the effects of rHuEpo therapy on cell-mediated immunity in hemodialysis patients, a prospective controlled study was conducted. Two parameters of immune function were tested. One was natural killer cell (NK) activity, and the other proliferation in response to the T cell mitogen concanavalin A (Con-A). NK activity of the ESRD patients was comparable with that of normal controls at the start of the study and was unaffected by rHuEpo therapy. In contrast to this, anemic ESRD patients initially demonstrated impaired mitogen driven proliferation (initial stimulation index (S.I.) = 42.5 +/- 11.9) which significantly improved following rHuEpo therapy (final S.I. = 73.3 +/- 14.7, p < 0.05). The later value exceeded the mitogen response in less anemic ESRD patients who did not receive rHuEpo (initial S.I. = 60.7 +/- 16.5, final S.I. = 61.0 +/- 16.7), but did not reach values seen in normal controls. The data suggest that rHuEpo therapy may be associated with enhanced immune responses in patients with ESRD.
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PMID:The effects of recombinant human erythropoietin on the cell mediated immune response of renal failure patients. 146 32

Erythropoietin (EPO) adjusts the red cell mass to the optimal size in order to satisfy the oxygen requirement of the body. The amount of circulating EPO is regulated by oxygen sensors in the kidney, which control the secretion of EPO through feedback signals. EPO stimulates the erythroid progenitor cells at different levels to develop into mature red blood cells. In anaemia, the serum EPO concentration, which is normally around 15 U/l, can increase 100-fold, or more. Patients with severe renal failure are unable to adapt the production of EPO in response to low haematocrit levels, and anaemia is due to a relative EPO deficiency. Studies have shown that recombinant human erythropoietin (r-HuEPO) could quickly correct anaemia in chronic renal failure by inducing a dose-dependent rise in haemoglobin and in the haematocrit level. r-HuEPO is now the standard treatment to correct severe anaemia in chronic renal failure. In recent years, r-HuEPO has been tested in other types of anaemia, some of which are fully discussed in this supplement together with various dosage regimens and routes of administration.
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PMID:Current and potential applications for erythropoietin. 157 62

Erythropoietin is a glycoprotein hormone that plays a vital role in erythropoiesis. It is mainly produced in the fetal liver till the third trimester of pregnancy. At that point, the kidney interstitium takes over this function and becomes the main source of erythropoietin. Hypoxia stimulates erythropoietin production by a mechanism that may require a heme protein as a second messenger. Erythropoietin stimulates the maturation of erythroid precursors (colony-forming unit-erythroid and burst-forming unit-erythroid) via at least two types of cell surface receptors. The higher-affinity receptors appear to be more important in modulating the effects of erythropoietin in vivo. Changes in intracellular calcium may ultimately mediate the action of erythropoietin on erythroid precursors. A specific and sensitive radioimmunoassay is now available for accurately measuring erythropoietin levels. All forms of erythrocytosis except polycythemia vera are associated with elevated erythropoietin levels. Levels are also high in cord blood obtained following fetal asphyxia. Reduced levels are seen in patients with anemia due to renal diseases. The response of erythropoietin to the degree of anemia appears to be attenuated in patients with cancer, chronic diseases, and human immunodeficiency virus (HIV) infection. Erythropoietin has been successfully used for treating patients with anemia due to renal failure. Its use has also been approved for the treatment of anemia patients receiving zidovudine for HIV infection. Encouraging results have been observed when erythropoietin was used to treat anemia due to rheumatoid arthritis, hematological malignancies, and prematurity. It has also been used to increase the yield of autologous blood collected prior to an elective surgical procedure. However, it has not proved to be useful in sickle cell anemia and myelodysplastic syndromes.
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PMID:Erythropoietin. Biology and clinical applications. 178 66

Recombinant human erythropoietin (epoetin) is a remarkably safe and effective biological product. Many dialysis patients are benefiting from the use of this drug when administered intravenously (IV) or subcutaneously (SC) three times a week. However, many patients are not receiving optimal therapy. Optimal therapy requires an understanding of the principles of effective usage and a definition of an optimal hematocrit (Hct) level. These therapeutic principles include (1) the erythroid response to epoetin is dose-dependent, but variable within a given dose; (2) the SC route of injection is as effective, if not more so, than IV injections; (3) the frequency of administration is route-dependent; (4) adequate iron stores are necessary for optimal response; (5) blood pressure may increase as the Hct increases, but may improve with time due to hemodynamic adjustments; (6) the anemia is primarily a hormone-deficiency state and not due to uremia; and (7) infections and traumatic (ie, surgical) inflammation may blunt the response to epoetin. Many patients with the anemia of renal failure have yet to benefit from treatment. These include patients with progressive renal failure or chronic transplant rejection, and dialysis patients who have had incomplete correction of their anemia.
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PMID:Erythropoietin 1991--an overview. 192 76

Mechanisms for the development of anemia and the effects of recombinant human erythropoietin (r-HuEPO) on hematological parameters were studied in new congenital adult type polycystic kidney (DBA/2FG-pcy) mice. The majority of DBA/2FG-pcy mice showed progressive anemia and an elevation of blood urea nitrogen, while a minority showed progressive anemia following polycythemia. Kidneys with numerous cysts in the cortex and medulla occupied virtually the entire abdominal cavity, and the combined kidney weight taken as a percentage of body weight reached 13.5% in the DBA/2FG-pcy mouse. The osmotic fragility of DBA/2FG-pcy mice erythrocytes was significantly increased compared with that of normal control mice. In addition, two-fold increases in serum EPO levels, determined by radioimmunoassay, and a decreased number of colony forming unit-erythroid (CFU-E) were observed in the DBA/2FG-pcy mice. The administration of r-HuEPO during anemia significantly increased the red blood cell count, hemoglobin concentration, hematocrit and reticulocyte percentage in a dose-dependent manner. These findings indicate that anemia in the DBA/2FG-pcy mouse is due to increased fragility of erythrocytes, a deficiency in EPO for the degree of anemia and a decreased number or a decreased response of erythroid progenitor cells. We suggest that the DBA/2FG-pcy mouse is a useful spontaneous model of chronic progressive renal failure.
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PMID:Anemia in new congenital adult type polycystic kidney mice. 194 61

The erythropoietic factors present in an anephric patient with nearly normal hematocrit were isolated from plasma by reversed-phase and gel permeation HPLC. The most active fraction was purified and the analysis of its N-terminal sequence was identical to the published sequence of the human insulin-like growth factor I (IGF I). Recombinant human IGF I had identical elution positions as the isolated erythropoietic factor on reversed-phase HPLC and the same molecular weight on gel permeation HPLC. Furthermore, hrIGF I stimulated erythroid colony formation in human bone marrow cultures as was previously shown for the isolated human erythropoietic factor. These results suggest that IGF I may replace erythropoietin as a stimulator of erythropoiesis in some patients with anemia and renal failure.
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PMID:The N-terminal sequence of the major erythropoietic factor of an anephric patient is identical to insulin-like growth factor I. 199 27


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