Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight young children with renal failure, undergoing continuous peritoneal dialysis (CDP) and presenting an anemia (hemoglobin level [Hb] 57 to 89 g/l) were treated by subcutaneous recombinant human erythropoietin (rHu EPO) twice weekly. The initial dose of 75 U/kg was adjusted to induce progressive increase of Hb with a target level of 100-120 g/l. Treatment duration was 24 weeks in five of these children and 10 to 13 weeks in the three others. In seven cases out of eight, anemia was corrected. The target Hb level was reached in 3 to 21 weeks with rHu EPO doses of 150 to 300 U/kg/w (mean: 200 U/kg/w) for four children without recent transfusion; then the median maintenance dose was 135 U/kg/w (range: 50-300 U/kg/w). In only one patient, Hb never reached a level higher than 77 g/l despite weekly dose of 350 U/kg, a reticulocytosis of 5.6%, rHu EPO treatment lasting up to 24 weeks and the absence of iron deficiency. In any case, no transfusion was necessary after the first day of rHu EPO treatment. In three patients, the increase of a preexisting hypertension required the adaptation of antihypertensive treatments. One patient presented a marked thrombocytosis. In conclusion, twice-a-week subcutaneous injections of 75 to 150 U/kg of rHu EPO appear to be well tolerated and effective in the treatment of anemia of CPD children.
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PMID:[Effectiveness of and tolerance to human recombinant erythropoietin in the treatment of kidney failure anemia in children undergoing continuous peritoneal dialysis. Multicenter study]. 777 95

The availability of recombinant EPO has greatly improved the lives of patients with end-stage renal disease. Knowledge is still accumulating regarding the use and effects of EPO in patients on PD, and several critical questions remain to be answered: 1. At what hematocrit level and when in the predialysis or dialysis course should EPO be started in PD patients? Recent studies by Golper suggest that the concomitant initiation of EPO and PD results in an increased hematocrit response compared to starting EPO after PD has been initiated for some time (63). 2. What is the best route of administration of EPO in PD patients? It is apparent that i.v., SC, and IP EPO can be effective in this population if utilized properly. The goal should be to tailor the route to the needs of the patient. Perhaps the daily SC route, for example, might be best for minimizing hypertension because of the slow, steady rise of hematocrit, while the IP route would be best tolerated by children (33,64). 3. What should the target hematocrit level be? This may vary depending on which organ function is being assessed. For the whole patient data are not currently available on appropriate hematocrit targets to maximize oxygen utilization, but near normal levels have recently been reported to be safe and beneficial (65-67). 4. What are the end-organ effects of anemia and its correction in PD patients? There is a dearth of information in this area for PD as well as HD patients. Additional research of this kind will increase our understanding of the pathophysiology of anemia as well as uremia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Erythropoietin treatment in peritoneal dialysis patients. 794 80

The aim of this study was to investigate the effects of recombinant human erythropoietin (rh-EPO) in patients with cancer-related anaemia. Thirty-six ambulatory patients who had malignant neoplasms and haemoglobin (Hb) values of < 11 g/dl (Pretoria is 1,310 m above sea level) entered the study. Patients with renal insufficiency or anaemia caused by bleeding or haemolysis, and patients with iron deficiency or megaloblastic anaemia, were not entered in the study. 22 IU/kg rh-EPO was given subcutaneously 3 times/week. The dose was escalated if Hb values did not rise after 4 weeks. All 36 patients were evaluable for toxicity. Side effects ascribed to rh-EPO were pain or discomfort at the site of injection (12 patients), heart palpitations (3 patients), skin rash (2 patients) and hypertension, deep vein thrombosis, and myalgia in 1 patient each. Thirty of the 36 patients who entered the study were evaluable for response. There were 16 females and 14 males among the evaluable patients. Median age was 64.5 years. Response, defined as an increase of Hb of at least 2 g/dl or to 12.5 g/dl, for at least 1 month, was documented in 12 patients. This was accompanied by an improvement in performance status and occurred within 1 month in 5 of the 12 patients who responded. rh-EPO has a limited but measurable therapeutic value for patients with cancer-associated anaemia.
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PMID:Recombinant human erythropoietin in the treatment of cancer-related anaemia. 797 Apr 93

Eleven children aged 0.6-17 years with preterminal chronic renal failure and anemia (mean serum creatinine concentration 4.8 mg/dl; mean hemoglobin concentration 7.9 g/dl) were treated with sc injections of recombinant human erythropoietin (EPO, initial dose 150 U/kg/week) over a mean period of 13 months. When a target hemoglobin concentration of 11.5-13.5 g/dl was reached, the dose was adapted. Iron deficiency was corrected. Hemoglobin concentration increased by > 2 g/dl in all patients within 14-119 (mean 45) days. The last maintenance dose ranged between 75 and 300 (mean 133) U/kg/week. No major adverse effects were observed, except for hypertension which occurred in about half of the patients and necessitated interruption of EPO in one child with advanced renal failure. Additional antihypertensive drugs were given to five patients. Body height increased in two patients by 0.6 and 1.3 SDS/year, respectively. In six patients with a mean observation period of 14 months before and 16 months after the start of EPO, the mean slope of the reciprocal serum creatinine concentration curve improved slightly (p = 0.05). The proposed schedule appears to be safe for the treatment of renal anemia in most pre-dialysis patients. Frequent monitoring of hemoglobin, blood pressure, serum creatinine and ferritin is required.
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PMID:Treatment of renal anemia by subcutaneous erythropoietin in children with preterminal chronic renal failure. 811 Nov 77

Intracellular free calcium concentration ([Ca2+]i) was examined in the platelets of 15 control subjects (NT), 6 predialysis patients with chronic renal failure (CRF), 17 patients on hemodialysis (HD), 20 patients on continuous ambulatory peritoneal dialysis (CAPD), 10 normotensive persons with genetic hypertension (GHT) and 8 essential hypertensive patients (EHT). Levels of [Ca2+] i in the platelets were measured by the fluorescent calcium indicator Fura-2. Resting [Ca2+] i in CRF and HD patients was higher than the value in NT and that in CAPD patients was similar to NT. rHuEPO significantly increased the level of [Ca2+] i in CRF and HD patients compared to those in NT. Under resting and EPO-stimulated conditions, the levels of [Ca2+] i in GHT and EHT were higher than those in NT. rHuEPO increased the levels of [Ca2+] i in the absence of extracellular calcium in NT, GHT and EHT. In addition, EPO-stimulated calcium influx in GHT and EHT was greater than that in NT. Thus, it appears that the mechanism of rHuEPO-induced hypertension may be mainly due to elevation of [Ca2+] i. EPO may contribute to the development of genetic hypertension.
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PMID:[Effect of recombinant human erythropoietin on cytosolic free calcium concentration in platelets]. 819 22

A multicenter study with recombinant human erythropoietin (rh-EPO) was carried out. Of 172 hemodialysis patients with anemia selected for the study from 20 hospitals and clinics, 77 were males and 95 females (mean age 53.9 years). A starting dose of 1,500 U of rh-EPO (Epoetin beta) was administered intravenously at the end of every dialysis session. If the efficacy was not acceptable, the dose was increased to 3,000 U. When the target hematocrit was achieved (30%), the total dose was decreased. The results of the study were excellent relative to those of other multicenter studies with regard to efficacy, safety, and changes in laboratory data. The incidence of hypertension was lower in our study compared with other reports because we used a low initial dose. The efficacy of rh-EPO therapy was determined earlier and more reliably by reticulocytes than by hematocrit or hemoglobin. Prompt iron supplement therapy is recommended with careful observation of serum iron and ferritin.
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PMID:Multicenter study with recombinant human erythropoietin. 849 99

In a controlled European multicenter study, clinical tolerance of subcutaneously administered recombinant human erythropoietin (rh-EPO) therapy and its influence on the course of illness in 362 hemodialyzed patients (162 males, 200 females) from 16 European dialysis centers was studied. Of these, 181 patients served as a control group in the first year and received rh-EPO therapy in the second year. Of the 837 adverse events that occurred, 277 were classified as serious and 560 as nonserious. Thirty-two deaths have been reported for the study population: 18 in the control group and 14 in the therapy group. The individual analysis of the serious adverse events including death demonstrates a protective effect of rh-EPO on the high-risk cardiovascular situation of dialysis patients. Hypertension was no problem, and under rh-EPO therapy an increase in resistance to infection was observed. Subcutaneous rh-EPO treatment might have an even better safety profile than intravenous application.
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PMID:Adverse events of subcutaneous recombinant human erythropoietin therapy: results of a controlled multicenter European study. 849

1. There is no experimental proof that renal insufficiency is a necessary condition for hypertension during erythropoietin treatment. 2. The present study compares the effect of 3 weeks treatment with r-hu EPO (50 i.u./kg) on systolic blood pressure (SBP), haematocrit and plasma cGMP in an animal model of chronic renal failure (remnant kidney model excision) and sham-operated rats. 3. Sub-total nephrectomy induced a significant fall in haematocrit and a significant increase in plasma creatinine levels. Treatment with r-hu EPO resulted in a significant haematocrit increase in uraemic as well as in non-uraemic rats. Despite this effect, r-hu EPO treatment had no effect on SBP in sham-operated rats. On the contrary, this treatment caused significant SBP elevation in uraemic rats; in these rats, SBP increase did not correlate with haematocrit increase. 4. Plasma cGMP concentrations were significantly higher in uraemic compared to sham-operated rats and were not modified by r-hu EPO treatment. 5. This study provides evidence that renal insufficiency in rats is a prerequisite for the development of hypertension during erythropoietin treatment.
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PMID:Uraemia is necessary for erythropoietin-induced hypertension in rats. 857 15

Treatment with human recombinant erythropoietin (r-EPO) can dramatically improve renal anemia, whereas it has been reported that such improved anemia may involve or worsen hypertension. When we administered a single dose of r-EPO at 9,000 units to 16 patients with end-stage renal failure requiring examination with a right cardiac catheter immediately before the introduction of dialysis, we measured cardiovascular dynamics and various vasoactive substances. The mean blood concentration of EPO was 3,035 units/ml 15 minutes after administration. As compared with the value of 107.6 +/- 3.2 mmHg obtained before administration, the mean arterial blood pressure significantly increased following the administration of r-EPO to 111.5 +/- 3.8 mmHg after 5 minutes, 112.4 +/- 4.2 mmHg after 10 minutes, 113.7 +/- 4.3 mmHg after 20 minutes, and 113.6 +/- 4.3 mmHg after 30 minutes (p < 0.05). The mean pulmonary arterial blood pressure tended to increase to 17.9 +/- 1.8 mmHg after 10 minutes from the level of 16.3 +/- 1.8 mmHg before administration (p = 0.096). The pulmonary vascular resistance index (PVRI) was 165.0 +/- 18.0 mmHg before administration and significantly increased to 193.2 +/- 19.0 and 199.0 +/- 16.6 dyn.S.cm-5.m2 after 10 and 30 minutes, respectively (p < 0.01, p < 0.05). The systemic vascular resistance index (SVRI) also significantly increased to 2,587 +/- 195 dyn.S.cm-5.m2 after 30 minutes from the level of 2,454 +/- 207 dyn.S.cm-5.m2 before administration (p < 0.05). Changes in SVRI showed a bimodal pattern, as with changes in PVRI. Angiotensin-II concentration significantly decreased to 13.7 +/- 4.4 pg/ml after 15 minutes from the level of 15.7 +/- 3.2 pg/ml before administration (p < 0.05). There were no significant changes in endothelin, prostaglandin, or adrenaline concentration after the administration of r-EPO. From these results, it was revealed that pulmonary intra-arterial administration of r-EPO has the acute effect of increasing pulmonary vascular resistance, thereby pointing to a direct effect of r-EPO in pulmonary vasoconstriction. Although no changes in vasoactive substances were observed in the present investigation, further studies with more sensitive measuring methods may be necessary.
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PMID:[Acute effects of human recombinant erythropoietin on cardiovascular dynamics and vasoactive substances]. 901 84

Hypertension complicating the therapy of renal anemia with rHU-EPO is characterized by an increase in total peripheral vascular resistance, but the mechanisms underlying arteriolar vasoconstriction remain unclear. To assess the role of altered cellular calcium metabolism, resting platelet cytosolic calcium was measured in 12 previously normotensive patients with end-stage renal disease before and after 12 weeks of EPO-therapy, after 12 weeks of combined antihypertensive pharmacotherapy of EPO-induced hypertension, and after 12 weeks of concurrent administration of EPO and indomethacin. Patients with EPO-induced hypertension showed a significant raise in platelet calcium by comparison with calcium levels prior to EPO (179 +/- 15 vs 120 +/- 8 nmol/l), and there was a positive correlation between their blood pressure and platelet calcium levels (r = 0.9, p < 0.001). Antihypertensive therapy of EPO-induced hypertension resulted in a reduction of blood pressure and a reduction of platelet calcium to near normal levels (128 +/- 6 nmol/l). The non-steroidal antiinflammatory drug indomethacin prevented EPO-induced hypertension and EPO-associated alterations in platelet calcium. The results of the present study suggest that EPO-induced hypertension might be related to altered cellular calcium homeostasis. If EPO therapy induces alterations in calcium metabolism not only in platelets but also in vascular smooth muscle cells, these changes in calcium influx may contribute to arteriolar vasoconstriction during EPO therapy.
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PMID:Hypertension induced by recombinant human erythropoietin (rHU-EPO) can be prevented by indomethacin. Pathogenetic role of cytosolic calcium. 911 97


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