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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of recombinant erythropoietin (r-HuEPO) is an effective treatment for the anaemia of chronic renal failure, but in some patients it has been accompanied by elevated blood pressure. This study focuses on seven patients with end-stage renal failure, managed on haemodialysis, who developed probable hypertensive encephalopathy with seizures during treatment with r-HuEPO. All made a full recovery. The events were not clearly related to the haemoglobin concentrations achieved, and four patients have subsequently been restarted on r-HuEPO therapy at a reduced dose, resulting in a slower increase in haemoglobin with no recurrence of episodes of severe hypertension. Close attention needs to be paid to blood pressure in patients commencing erythropoietin therapy, and it seems prudent to aim for a gradual increase in haemoglobin concentration to allow the circulation to adapt to changes in oxygen delivery and haematocrit.
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PMID:Seizures in haemodialysis patients treated with recombinant human erythropoietin. 251 27

Studies were directed to characterization of the anaemia of renal failure of 11 patients on haemodialysis and determination of the way in which it is corrected by human erythropoietin derived from recombinant DNA expressed in Chinese hamster ovary cells (r-HuEPO) administered intravenously. Erythrokinetics before treatment showed that total red cell mass was below normal and that both erythron transferrin uptake and red cell survival were modestly reduced; treatment increased both total red cell mass and erythron transferrin uptake but did not change red cell survival in previously untransfused patients. When BFU-e and CFU-e from patient bone marrow were cultured in autologous serum we found no evidence for inhibitors of erythroid progenitor maturation in patient serum compared with normal. Erythroid expansion in response to r-HuEPO was not limited by the availability of iron, iron requirements for new red cell formation being met from stores (if adequate) or from oral iron supplements. In pharmacokinetic studies the plasma clearance of r-HuEPO could be expressed by a three-parameter exponential curve with T1/2 range of 2.3 to 7.3 h. T1/2 after the first dose of r-HuEPO was not significantly different from that after 14 to 54 weeks treatment when the erythron had expanded to a new steady state. Erythron transferrin uptake before treatment was related to endogenous production of erythropoietin estimated from the plasma clearance of the first dose of r-HuEPO administered intravenously. This finding suggested that the availability of erythropoietin was the main factor limiting expansion of the erythron. This conclusion was supported by the continuity of the relationship during the response to treatment.
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PMID:Characterization of the anaemia of chronic renal failure and the mode of its correction by a preparation of human erythropoietin (r-HuEPO). An investigation of the pharmacokinetics of intravenous erythropoietin and its effects on erythrokinetics. 259 53

The authors investigated the influence exerted on some lymphocyte and granulocyte functions during treatment with human recombinant erythropoietin in five female patients with renal failure due to chronic interstitial nephritis, who were included in a regular dialyzation programme. The authors revealed a significant increase of the candidacidal capacity of phagocytizing cells of the peripheral blood stream and an increased capacity of blastic transformation of lymphocytes after stimulation with the mitogen phytohaemagglutinin. In these changes the improved oxygen metabolism may participate by a correction of anaemia, when this preparation is administered, but it cannot be ruled out that erythropoietin interferes by some hitherto unknown mechanism with immune processes.
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PMID:[The effect of erythropoietin on lymphocyte and granulocyte functions in dialyzed patients]. 259 45

Several factors contribute to the pathogenesis of anemia due to renal failure. Hypoproliferation of red cell progenitors may be caused partially by an inhibitory effect of some 'uremic toxins' whose existence certainly is very controversial. Iron deficiency due to gastrointestinal and dialysis-related blood losses and occasionally aluminum intoxication may interfere with the maturation of the erythron. Moderate hemolysis with shortening of red cell survival to some 50% of normal may be an additional factor. The main cause of anemia is, however, inadequate production of erythropoietin by the diseased kidney. This latter factor has now become amenable to treatment.
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PMID:[Pathogenesis of anemia due to kidney disease]. 264 77

Over the past decade experimental haematologists have identified and eventually characterised a number of polypeptide growth factors capable of stimulating the proliferation and differentiation of haemopoietic progenitor cells in vitro. The molecular cloning of these growth factors has now allowed their use in vivo, and some of them have shown promise in recent clinical trials. Most of the work has been done on erythropoietin and myeloid growth factors, which are discussed in this review. Erythropoietin has been used successfully as replacement therapy in the anaemia of end-stage renal failure, but may also prove clinically useful in other chronic anaemias and, in combination with other growth factors, as a stimulant of bone marrow regeneration following bone marrow transplant. Myeloid growth factors, and, in particular, granulocyte colony-stimulating factor, have been shown to accelerate neutrophil recover in cancer patients following chemotherapy, with a reduction in the number of severe infections and mucositis.
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PMID:Clinical use of haematopoietic growth factors. 265 Jul 78

One of the most important deficiency states associated with chronic renal failure is profound anemia. While it has been possible to identify differing types of anemia in patients receiving dialysis support, and thus correct the secondary causes, most patients continue to exhibit symptoms and signs of the anemic state. This review of the anemias associated with renal failure explores the diagnostic and therapeutic possibilities that may help the physician in evaluating the anemic patient with chronic renal failure. Also described is the early clinical experience with a new genetically engineered hormone, recombinant human erythropoietin (r-HuEPo), which has been under investigation for nearly two years at The Cleveland Clinic Foundation as part of a multi-center trial. An orderly approach to the anemic patient with renal dysfunction is suggested, and conjectures about the impact of newer therapies are made.
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PMID:The anemia of chronic renal failure. Overview and early erythropoietin experience. 265

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.
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PMID:Hematologic aspects of renal insufficiency. 267 32

Fourteen nondialyzed patients with chronic renal insufficiency (serum creatinine 265 to 972 mumol/L [3.0 to 11.0 mg/dL]) and severe anemia (hematocrit less than 30%) were randomized to receive either recombinant human erythropoietin (r-HuEPO) or a placebo subcutaneously thrice weekly for 12 weeks or until reaching a hematocrit of 38% to 40%. Anemia was significantly ameliorated in the treated patients. No acceleration in the progression of renal failure (1/serum creatinine v time) or change in serum potassium was noted for either the placebo or treated group over the 12-week period. Six of seven treated patients had a significant decrease in serum ferritin and percent transferrin saturation (plasma iron/total iron-binding capacity). This resulted in functional iron deficiency and the requirement for iron supplementation. The average systolic and diastolic blood pressure did not differ significantly between the two groups of patients during the study. Quality of life was improved in all r-HuEPO-treated patients but not in those in the placebo group. This study demonstrates the safety and efficacy of r-HuEPO in the correction of anemia in predialysis patients without adverse effects on renal function over a 12-week period. Improved patient well-being as a result of the correction of anemia resulted in one patient refusing appropriate initiation of dialysis therapy.
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PMID:The use of recombinant human erythropoietin in the correction of anemia in predialysis patients and its effect on renal function: a double-blind, placebo-controlled trial. 268 5

The eventual commonplace use of recombinant human erythropoietin (r-HuEPo) for the treatment of the anemia associated with chronic renal failure will have definite consequences in the dialysis supported patient. The effect of this nonanemic state on renal transplantation, both in the early posttransplant period as well as the waiting period, was examined in this study. Thirteen of 16 patients who were treated with the hormone and subsequently underwent cadaveric renal transplantation (Tx) were compared to control transplant patients from a typical chronic renal patient population. There seemed to be no difference in the length of hospital stay, need for dialysis support post-Tx, or severity of acute post-Tx renal failure as measured by the days of dialysis support given. Furthermore, there seemed to be no evidence of marrow unresponsiveness to endogenous erythropoietin produced by the functioning allograft, so that after an initial fall in hemoglobin and hematocrit, these parameters returned to normal levels at three to six months. HLA antibody production was also tracked over the course of chronic r-HuEPo therapy, and the response followed one of three patterns: (a) initially very high (100%) or very low (less than 15%) and showed no change; (b) moderate to high reactivity fell to lower levels with time; or (c) some stimulation noted without recent blood transfusions. Thus, patients entering end-stage renal failure without having been exposed to transfusions can be maintained in a low antibody state and perhaps increase the cadaveric kidneys available to them. Therefore, r-HuEPo therapy in patients who will subsequently undergo transplantation seems to have no deleterious effect on patient morbidity, or transplant outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal transplantation: results in hemodialysis patients previously treated with recombinant human erythropoietin. 268 20

To examine the effects of erythropoietin on the anemia of chronic renal disease and on the rate of renal deterioration, we administered recombinant human erythropoietin to 17 patients with anemia and progressive renal failure who did not yet require dialysis (serum creatinine level, 353 to 972 mumol per liter [4.0 to 11.0 mg per deciliter]). The dose of erythropoietin (50 to 150 units per kilogram of body weight) was adjusted according to the hematocrit response. In all 17 patients the anemia responded to erythropoietin. The median hematocrit increased from 0.27 to 0.37. The rate of the response depended on the initial erythropoietin dose and was similar to that observed in patients who were on dialysis. Hypertension was present in 14 patients before therapy, developed during therapy in 2 of the normotensive patients, and worsened in 9 patients, who required additional antihypertensive medications. The rate of the decline in renal function, as measured by serial determination of the reciprocal of the serum creatinine level, did not change significantly as the hematocrit rose (P = 0.78 by the paired t-test) during erythropoietin therapy. All the patients reported improvements in appetite, activity level, and sense of well-being. We conclude that erythropoietin therapy is effective in correcting the anemia of patients with progressive renal failure without affecting renal function, although it may be associated with an increase in blood pressure.
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PMID:Treatment of the anemia of progressive renal failure with recombinant human erythropoietin. 274 47


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