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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the pathophysiology of hypertension in patients receiving recombinant human erythropoietin (rHuEpo) we studied its effects on the renin-aldosterone axis of chronic haemodialysis (HD) patients not receiving antihypertensive drugs. Nine severely anaemic normotensive HD patients received rHuEpo 50 U/kg bodyweight, thrice weekly after each HD. The dose was increased by 25 U/kg bodyweight every 4 weeks to a maximum of 100 U/kg or until an increase of Hb or Hct of 2 g/dl or 7% was achieved. Blood samples were taken after 30 min supine rest and while seated 10 min later after gentle ambulation. Results expressed as mean +/- SEM: therapy in normotensive HD patients by a negative feedback loop, before the development of hypertension.
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PMID:Suppression of the renin-angiotensin-aldosterone axis with erythropoietin therapy by a negative feedback loop. 131 71

Although erythropoietin (Epo) is known to correct anaemia in dialysis and pre-dialysis patients, there is limited experience with its use in immunosuppressed patients suffering from chronic renal graft dysfunction. We report the results of a pilot study of Epo in seven patients with failing grafts and normocytic normochromic anaemia attributable to renal failure. All entering patients had controlled blood pressure and serum ferritin greater than 100 micrograms/l. Three patients were taking triple immunotherapy (prednisone/azathioprine/cyclosporin), two patients prednisone/azathioprine, and two patients CsA monotherapy. Study duration mean was 15 +/- 2 (SEM) weeks, and Epo was started at 4000 units subcutaneously (s.c.) once weekly, adjusted to achieve a target haemoglobin (Hb) of 100 g/l. Mean Hb at initiation was 68 +/- 5 g/l and significantly increased to 96 +/- 6 at end of follow-up, P less than 10(-4). All patients responded. Maintenance Epo dosage was 120 +/- 32 U/kg bodyweight/week, roughly 4000 units/week. There was no significant change in serum creatinine: pre-study 392 +/- 45 mumol/l; post-study 430 +/- 62 mumol/l. There were no complications but blood pressure did rise significantly: pre- 124 +/- 11/74 +/- 4 mmHg to post- 142 +/- 10/86 +/- 3, P less than 0.05 for systolic and diastolic. Low-dose s.c. Epo effectively corrects anaemia in graft failure despite azathioprine and/or CsA therapy, without obvious acceleration of graft failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-dose subcutaneous erythropoietin corrects the anaemia of renal transplant failure. 131 75

Anaemia is a feature almost invariably complicating chronic renal failure. Its pathophysiology is multifactorial but the most important cause is erythropoietin (Epo) deficiency. However, either no relation or even a weakly positive relation generally exists between serum immunoreactive (i) Epo and haematocrit values in uraemic anaemia, whereas in anaemias of non-renal origin the correlation is most often strongly negative. Recent evidence indicates that growth hormone also stimulates erythropoiesis. Moreover, late erythroid progenitor cells (CFU-E) require insulin and/or insulin-like growth factor I (IGF-I) for development in vitro. IGF-I has been shown to have a synergistic action with Epo. We have measured serum iEpo and IGF-I levels in 17 haemodialysis patients with severe hyperparathyroidism (mean +/- SEM serum iPTH, 988 +/- 88 pg/ml). Mean age and duration of dialysis treatment were 46.1 +/- 3.4 and 8.8 +/- 1.0 years respectively. Mean haematocrit and haemoglobin values wer 28.1 +/- 1.7% and 9.39 +/- 0.54 g/dl respectively. Mean serum iEpo and IGF-I levels were 20.3 +/- 4.7 mU/ml and 320 +/- 20 ng/ml respectively (normal values for serum iEpo and IGF-I, 17.9 +/- 6 mU/ml and 91 +/- 23 ng/ml respectively). We found that serum IGF-I concentrations were well correlated with haematocrit values (r = 0.68, n = 15, P less than 0.004) whereas serum iEpo values were not (r = 0.41, n = 12, P = 0.18). IGF-I could therefore be an important factor regulating erythropoiesis in uraemic patients, at least when associated with severe hyperparathyroidism.
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PMID:Insulin-like growth factor I: a modulator of erythropoiesis in uraemic patients? 131 79

This study examines the response in plasma erythropoietin values to haemorrhage of 20% of the estimated blood volume in chronically cannulated ovine fetuses, of gestational ages 128-144 days. Blood samples were collected at 0, 2, 4, 6 and 24h with respect to the haemorrhage. In 5 control experiments there was no significant change in plasma erythropoietin concentration, across this time period, values being 6.1 +/- 2.3 and 6.4 +/- 2.4 mU/ml at 0 and 24h respectively. Values are mean +/- SEM. Haemorrhage reduced the haematocrit and haemoglobin values, significantly, to 83 +/- 6% and 85 +/- 4% (n = 5) of the initial value, respectively, but did not cause a statistically significant increase in plasma erythropoietin concentrations (7.2 +/- 2.4 and 20.7 +/- 8.2 mU/ml; P = 0.131). A larger degree of haemorrhage, in four fetuses reduced the haematocrit to 64 +/- 2.8% of initial, over 24-54h and increased erythropoietin values very significantly (from 11.9 +/- 3.6 to 91 +/- 8.3 mU/ml; P = 0.001).
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PMID:The effect of haemorrhage on erythropoietin concentration in the mature ovine fetus. 132 76

Physical performance and haemodynamic parameters at rest and with exercise were compared in a prospective, cross-over fashion in 12 anaemic haemodialysis patients (Hb 6.4 +/- 0.5, mean +/- SEM) at two levels of haemoglobin (Hb 9 and 12 g/dl) before and after long-term treatment with recombinant human erythropoietin (rHuEpo). Patients were divided into two groups and measurements made prior to treatment, upon reaching, and after 4 months at the first target Hb (9 g/dl group A, 12 g/dl group B), and after 4 months at the alternative target Hb. Tests included an exercise radionuclide ventriculogram, Doppler echocardiogram, and respiratory function exercise test. Compared to pretreatment, there was a significant reduction in resting pulse rate (P < 0.001), and in pulse rate (P < 0.001) and arterial lactate (P < 0.01) concentrations at specified levels of exercise. Work capacity improved 60% (P < 0.001), and left ventricular mass fell by 26% (P < 0.001). Although cardiac output (CO) during and after exercise was reduced (P < 0.05), resting CO, cardiac index, stroke volume and ejection fraction (rest and exercise) were not significantly altered. There appeared little benefit in having the higher target Hb: no significant difference could be found between target levels for almost any measure. In addition, despite marked improvement from pretreatment levels, performance parameters were still below those of non-uraemic age-matched controls. These results demonstrate the beneficial but incomplete effect of rHuEpo on resting and exercise-related factors, and suggest that most improvement is achieved with modest increments in haemoglobin.
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PMID:Haemodynamic changes and physical performance at comparative levels of haemoglobin after long-term treatment with recombinant erythropoietin. 133 60

Left ventricular size and function were evaluated in 15 anemic chronic hemodialysis patients before and after the administration of recombinant human erythropoietin (rHuEPO). All patients were studied with two-dimensional and M-mode echocardiographic examinations before the initiation of rHuEPO (T1) and at 28 +/- 7 weeks of rHuEPO therapy (T2). The two-dimensional targeted M-mode echocardiographic measurements obtained were: end-diastolic dimension (EDD); end-systolic dimension (ESD); stroke dimension (SD); dimensional shortening (SD/EDD); systolic posterior wall thickness (PWs); diastolic posterior and interventricular septal thickness; end-systolic wall stress (ESWS); and left ventricular mass. Mean hematocrit in these patients increased almost 50%. The EDD decreased from a mean value (+/- SEM) of 6.41 +/- 0.33 to 4.93 +/- 0.21 cm (p less than 0.05). ESD decreased from a mean value of 4.16 +/- 1.2 to 2.77 +/- 0.06 cm (p less than 0.05). The calculated mean SD decreased slightly but not significantly from 2.21 +/- 0.69 to 2.19 +/- 0.60 cm. The calculated SD/EDD increased from a mean 0.35 +/- 0.09 to 0.44 +/- 0.07 (p less than 0.05). ESWS fell from 59.2 +/- 12.2 to 37.6 +/- 9.3 gm/cm2 (p less than 0.01), and left ventricular mass fell (p less than 0.05) from 347 +/- 15.2 to 227 +/- 59 gm. There was no significant difference in resting heart rate or systolic blood pressure between T1 and T2. The increase in dimension shortening reflects afterload reduction, as indicated by the fall in end-systolic wall stress.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in left ventricular size, wall thickness, and function in anemic patients treated with recombinant human erythropoietin. 138 84

The quality of life of 12 hemodialysis (HD) patients was assessed in a prospective, blinded, cross-over fashion before treatment with recombinant human erythropoietin (r-HuEPO) and at two different levels of hemoglobin (Hb, 9 and 12 g/dl) by means of an interviewer-based questionnaire, the sickness impact profile (SIP). Patients were matched into two groups with no significant difference for age, weight, Hb (6.3 +/- 0.5, mean +/- SEM, group A, vs. 6.4 +/- 0.9 group B), length of hemodialysis or number of years of prior transplantation. SIP was assessed prior to treatment, after reaching the first target Hb (Hb 9 g/dl group A, 12 g/dl group B), after 4 months at that target Hb and after 4 months at the alternative target Hb for each group. For all patients, there was a highly significant improvement in quality of life as assessed by lower SIP scores between the initial and second assessments. This was evident for the physical (8.9 +/- 1.4 vs. 2.8 +/- 1.0; p less than 0.001) and psychosocial (14.9 +/- 3.9 vs. 4.4 +/- 1.1; p less than 0.01) dimensions. Total scores (16.3 +/- 2.4 vs. 5.7 +/- 0.9; p less than 0.001) showed similar changes, reflecting significant improvement in 10 of 12 possible categories between the first two assessments (p less than 0.05 to p less than 0.001). Improved scores were maintained but did not change appreciably after the 2nd assessment. There was no significant difference in any score (category, dimensional or total) obtained after 4 months at Hb 9 g/dl compared to those after the same period at Hb 12 g/dl.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Subjective quality of life assessment in hemodialysis patients at different levels of hemoglobin following use of recombinant human erythropoietin. 141 77

This study attempts to evaluate the adequacy of the erythropoietin (EPO) response in 42 anaemic patients with advanced human immunodeficiency virus (HIV) infection [30 with acquired immunodeficiency syndrome (AIDS) and 12 with AIDS-related conditions] by comparing their serum EPO levels with those found in a non-HIV reference population consisting of 36 patients with anaemia of chronic disorders (ACD) and 57 with iron deficiency anaemia (IDA). Although the average Hb concentration was similar in the three groups, the EPO level for HIV patients (mean +/- SEM, 64.3 +/- 7.7 mU/ml) did not differ significantly from that in ACD patients (45.3 +/- 8.3 mU/ml, P > 0.1), and both groups had a lower mean EPO level (P < 0.05 and P < 0.01 respectively) than IDA subjects (133.5 +/- 18.7 mU/ml). Thirteen HIV patients on zidovudine therapy showed similar mean Hb and EPO levels to those in the untreated patients. A significant inverse correlation between the log of serum EPO and the Hb values was observed in the three groups. However, this relationship was found to be stronger in IDA patients than in either HIV or ACD subjects (P < 0.001), with no difference between the two latter groups (P > 0.2). These data suggest that the EPO response is blunted in the anaemia associated with advanced HIV infection.
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PMID:Serum erythropoietin levels in anaemic patients with advanced human immunodeficiency virus infection. 148 42

Eleven anemic children and adolescents with a median age of 14 years (range six months-20 years) on chronic hemodialysis were treated with recombinant human erythropoietin (rHuEPO) intravenously three times a week for an average of 9.2 months. After eight weeks of therapy, hematocrit rose from 20.3 +/- 1.4% to 31.7 +/- 0.7% (0.20 +/- 0.01 to 0.31 +/- 0.007, p less than 0.001, mean +/- SEM). After reaching the target hematocrit of 30% to 33% (0.30 to 0.33), doses were adjusted individually. Blood transfusions were eliminated in all but one patient. All patients experienced an increase in appetite and energy level. Serum ferritin concentrations decreased in all patients who reached target hematocrit and seven required iron supplementation. Hypertension worsened in two patients and developed in two others. One patient's vascular access clotted. Dialysis efficiency and heparin requirements during dialysis did not change significantly. We conclude that rHuEPO is safe, effective, and should be recommended as treatment for anemia in children and adolescents on hemodialysis, but close monitoring for the development of hypertension and/or iron deficiency is necessary.
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PMID:Therapy of renal anemia in children and adolescents with recombinant human erythropoietin (rHuEPO). 154 82

Newborn infants of diabetic mothers have serum biochemical signs of iron deficiency in cord blood directly related to elevations of cord erythropoietin and Hb concentrations. In sheep, chronic fetal hyperinsulinemia results in fetal hypoxemia, expansion of the red cell mass, and decreased iron concentrations, most likely due to increased iron utilization for Hb synthesis. To determine whether fetal insulin exposure also results in reduced tissue iron concentrations, we measured liver, skeletal muscle, small intestine, heart, and brain iron concentrations in newborn rat pups after s.c. fetal injection of insulin or diluent alone on d 19 of gestation. The fetuses of 11 pregnant rats were exteriorized, injected with 2 U neutral protamine Hagedorn insulin or diluent, replaced in utero, and delivered on d 22. To determine dose dependency, the fetuses of six pregnant rats were injected with 3 U of longer-acting protamine zinc insulin and delivered on d 21. At delivery, the insulin-treated groups had higher birth weights than the placebo-treated group, although plasma insulin concentrations were not different. The 2 U neutral protamine Hagedorn insulin-treated fetuses had significantly lower mean +/- SEM liver iron concentrations than the control fetuses (910 +/- 34 versus 1014 +/- 43 micrograms/g dry tissue weight; p less than 0.05), but had similar skeletal muscle iron concentrations. The 3 U protamine zinc insulin-treated fetuses had significantly lower liver and skeletal muscle iron concentrations compared to control and to 2 U neutral protamine Hagedorn insulin-treated fetuses (p less than 0.05). No differences in small intestine, heart, or brain iron concentrations were seen among groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of in utero insulin exposure on tissue iron status in fetal rats. 159 33


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