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)

Ten patients with end-stage renal failure and anaemia (mean haemoglobin 6.1 g/dl, range 4.6-8.8 g/dl) on thrice-weekly haemodialysis were treated with human erythropoietin derived from recombinant DNA (rHuEPO). This was given as an intravenous bolus after each dialysis in rising doses within the range 3-192 IU/kg. All patients showed increases in reticulocyte numbers and haemoglobin concentration and after the first week of treatment none of the four previously transfusion-dependent patients needed further transfusions. In nine patients treated for 12 weeks haemoglobin rose to a mean of 10.3 g/dl, range 9.5 to 12.8 g/dl. Thereafter the dose of erythropoietin was adjusted to avoid a further rise in haemoglobin. During treatment one patient had an episode of hypertensive encephalopathy and two had clotting in their arteriovenous fistulas (complete in one). rHuEPO is an effective treatment for the anaemia of end-stage renal failure but longer-term observations are needed on the consequences of increasing the haematocrit.
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PMID:Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. 287 23

Recombinant human erythropoietin is a major advance in the management of patients with chronic renal failure. The sustained dose-dependent rise in haematocrit which it produces effectively abolishes symptoms of anaemia, but at the cost of an increase in blood viscosity. This in turn predisposes to increased vascular resistance and the development of hypertension. Over half of all deaths of patients with end-stage renal failure are from cardiovascular disease, notably myocardial infarction, heart failure, and stroke, for which hypertension is a known risk factor. Erythropoietin-related increases in blood pressure are therefore of particular concern, and seem to be most severe in previously hypertensive patients. There is now a need to establish the optimum rate and extent of rise of haematocrit required to alleviate symptoms without incurring undue risk.
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PMID:Hypertension, blood viscosity, and cardiovascular morbidity in renal failure: implications of erythropoietin therapy. 289 90

Hemodynamics were evaluated in 8 patients with uncomplicated renal failure on regular dialysis before and after partial correction of anemia by treatment with recombinant human erythropoietin (r-huEPO). Under r-huEPO treatment, mean (+/- SD) hemoglobin increased from 7.51 (0.60) to 10.27 (0.92) g/dl. Mean blood pressure, body weight, total blood volume and extracellular fluid compartment remained unchanged. Cardiac output as measured with a radionuclide method increased significantly from 4622 (1069) to 5393 (1285) units (p less than 0.02) and peripheral resistance decreased from 22 (4) to 19 (3) units (p less than 0.02). 6-keto-1-alpha-prostaglandin decreased from 96.9 (54.4) to 61.6 (18.0) pg/ml (p less than 0.05) but plasma renin activity, noradrenalin and atrial natriuretic peptide remained unchanged comparing pre- and post-treatment levels. This observation suggests that an increase of red blood cell mass can improve heart function in patients undergoing regular dialysis treatment.
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PMID:Hemodynamics of patients with renal failure treated with recombinant human erythropoietin. 291 12

Twelve anaemic patients on haemodialysis were treated with recombinant human erythropoietin, starting with 72 IU/kg/week. The dose was doubled after 2 weeks until an increase of 2 g/dl of haemoglobin was observed. The effects on various parameters were studied during a 3-month period. Haemoglobin increased from 6.70 +/- 0.74 to 10.49 +/- 1.04 g/dl (mean +/- SD, P less than 0.001), potassium from 5.51 +/- 0.50 to 6.06 +/- 0.65 mmol/l (P less than 0.005), phosphate from 1.78 +/- 0.40 to 2.17 +/- 0.40 mmol/l (P less than 0.001) and the calcium phosphorus product from 4.3 to 5.2 (P less than 0.001). Three patients developed marked periarticular inflammation due to calcified deposits with a high calcium-phosphorus product of 6.8. An increase in arterial blood pressure was observed in three previously well-controlled hypertensive patients, one of whom developed hypertensive encephalopathy. We conclude that recombinant human erythropoietin is very effective in treating the anaemia of end-stage renal failure on haemodialysis. Regular estimations of serum potassium and phosphate are mandatory. In hypertensive individuals a further increase in blood pressure is possible.
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PMID:Human recombinant erythropoietin in anaemic patients on maintenance haemodialysis. Secondary effects of the increase of haemoglobin. 314 24

Recombinant human erythropoietin (r-HuEPO) was administered in two phases to 12 patients with chronic renal insufficiency (creatinine clearances of 0.17-0.51 ml/second [10-30 ml/minute]) and uremic anemia. In addition to the routine tests done as part of a multicenter clinical trial, our patients had serial red cell mass measurements, quantitation of bone marrow stem cells, and marrow cytogenetic analysis. During the first eight weeks (acute phase), an equal number of patients was randomized to placebo or one of three doses of r-HuEPO (50, 100 or 150 unit/kg intravenously three times weekly). All three patients receiving 150 unit/kg responded by increasing their packed cell volume (PCV) to the normal range within eight weeks. There were lesser responses in PCV at the two lower doses of r-HuEPO and no response in the placebo group. The 51Cr red cell mass also increased significantly in a dose-related manner in patients receiving r-HuEPO but did not change in the placebo group. Marrow studies revealed increases in erythroid, megakaryocyte, and granulocyte-monocyte progenitor cells in those patients on r-HuEPO, but no mutagenic effects were seen. Subsequently, ten patients received open label r-HuEPO. During this maintenance phase, all ten achieved or maintained a normal PCV. Several adverse events occurred, but none were definitely linked to r-HuEPO. Recombinant human erythropoietin is an effective and potent treatment of anemia caused by renal failure.
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PMID:Treatment of the anemia of predialysis patients with recombinant human erythropoietin: a randomized, placebo-controlled trial. 317 33

The concentration of human marrow progenitors CFU-E, BFU-E, CFU-GM, and CFU-Mk and the percentage of these progenitor cells in DNA synthesis were studied in nine patients with transfusion-dependent anemia of end-stage renal failure before and 2 weeks after treatment with human recombinant erythropoietin (Epo) at a dose of 150 to 300 U/kg intravenously three times per week. The concentration of CFU-E in the posttreatment marrow increased by a mean of 4.15-fold, BFU-E by 3.37-fold, CFU-GM by 1.86-fold, and CFU-Mk by 1.96-fold as compared with their respective concentrations in the pretreatment marrows. This increase in the concentrations of marrow progenitors was accompanied by almost a doubling of the percentage of these cells in DNA synthesis as assessed by the 3H-thymidine suicide technique. These observations demonstrate that at the progenitor cell level the human marrow responds to therapeutic doses of Epo as an organ rather than by a selective expansion of the erythroid cell line.
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PMID:Effects of recombinant erythropoietin on the concentration and cycling status of human marrow hematopoietic progenitor cells in vivo. 319 79

The response of bone marrow and peripheral blood erythroid progenitors to human recombinant erythropoietin (rHuEPO) was studied in nine haemodialysed renal failure patients receiving this hormone for the correction of their anaemia. The haematocrit rose in all patients in response to thrice weekly injections of escalating rHuEPO doses (12-192 IU/kg). Both the numbers of CUF-e and BFU-e and their proliferative state in the bone marrow as well as BFU-e numbers in the peripheral blood were estimated before treatment and again after correction of the anaemia, at 16 h following an intravenous dose of rHuEPO. Following treatment bone marrow BFU-e numbers fell to a mean of 24.5% (P less than 0.01) of the pre-treatment values although there was no significant change in CFU-e or circulating BFU-e numbers. The mitotic rate (percentage S-phase cells) estimated by tritiated thymidine suicide rose from 45.2% to 68.4% (P less than 0.05) in the case of CFU-e and from 16.4% to 45.1% (P less than 0.05) for BFU-e following treatment with rHuEPO thus indicating in-vivo sensitivity of both the primitive as well as the mature erythroid progenitors to the hormone. The fall in BFU-e numbers in the bone marrow after several months of treatment may be due to a loss of cells from this progenitor pool by maturation that is uncompensated by replacement from the pluripotential stem cell compartment.
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PMID:Erythroid progenitor cell kinetics in chronic haemodialysis patients responding to treatment with recombinant human erythropoietin. 320 31

The pathophysiology of anemia associated with renal failure and the major pharmacologic agents used in the treatment of this anemia are reviewed. Patients with renal failure are often anemic primarily because of diminished circulating erythropoietin and suppressed erythropoiesis in the bone marrow. The anemia may cause malaise, fatiguability, aggravated angina, and decreased exercise tolerance. Many patients require frequent red blood cell transfusions. Therapy has included anabolic androgen administration, iron and vitamin supplementation, and the administration of red blood cells. These approaches generally have not resulted in sustained improvement of the anemia. The recent development of recombinant human erythropoietin may represent a major therapeutic advance for the treatment of anemia associated with renal failure. Previously, erythropoietin therapy was not possible because of lack of sufficient quantities of the purified hormone. Clinical trials indicate, however, that recombinant human erythropoietin may improve erythropoiesis in most patients. Adverse effects have generally been mild and easily managed; however, increases in blood pressure and arteriovenous fistula clotting have been reported. Although initial reports are encouraging, larger and longer clinical trials are needed to determine proper dosing and to understand more completely the potential adverse effects of recombinant human erythropoietin. Previous pharmacologic attempts to improve the anemia associated with renal failure have been largely unsatisfactory; initial reports on the use of recombinant human erythropoietin are promising.
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PMID:Pathophysiology and treatment of the anemia of renal failure. 328 Feb 18

Post-transplant erythrocythemia (PTE) is a common finding in renal allograft recipients, although the etiology of this disorder has not been clearly established. We identified 22 patients (9.8%) with PTE from among 225 renal transplant recipients followed for an average of 5.5 years. To characterize possible predisposing factors and to study the clinical significance of PTE, these patients were compared with a control group matched for age, race, sex and etiology of renal failure. Plasma volume (PV) and red blood cell mass (RBCM) were measured in the majority of patients with PTE. Peripheral serum erythropoietin (Ep) levels were determined in the majority of patients in the control and PTE groups. PTE occurred an average of 11.4 months after transplantation. Risk factors for the development of PTE were pretransplant hypertension, retention of native kidneys, higher pretransplant hematocrit, and diuretic use for treatment of post transplant hypertension. Ep levels in the PTE and control groups were not significantly different. Twenty of the 22 patients with PTE were receiving concurrent diuretic therapy, and hematocrits fell to normal levels in all of these patients following cessation or dose reduction of diuretic. No other treatment of PTE was utilized, excluding the phlebotomy of a single unit of blood from one patient. No thromboembolic complications were noted during the follow-up period. We conclude that PTE is frequently induced by overzealous diuretic therapy for treatment of post-transplant hypertension. Discontinuation or reduction of diuretic therapy results in resolution of PTE in nearly all patients. From this experience we have developed an algorithm for the investigation and management of PTE.
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PMID:Erythrocythemia following renal transplantation: influence of diuretic therapy. 328 31

Renal diseases are associated with a host of hematologic abnormalities affecting erythropoiesis, thrombopoiesis, platelet function, coagulation, fibrinolysis, and immune function. Many of the abnormalities described in acute or chronic renal failure appear to be directly related to accumulation of uremic toxins, particularly those in the middle molecular range and may respond to dialysis treatment. The recent availability of recombinant human erythropoietin facilitated the demonstration that anemia in renal failure is predominantly due to inadequate production of erythropoietin, and evolution in the management of anemia in these patients is now likely. Renal cell carcinoma is associated with a variety of unusual hematologic manifestations that may be confused with other diseases, but when recognized provide an early clue to the presence of a renal tumor and result in successful therapy.
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PMID:Hematologic abnormalities in patients with renal diseases. 330 22


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