Erythropoietin hypertension with

Erythropoietin (Eprex ) is physiologically produced in the kidney and regulates proliferation of committed progenitors of red blood cells. It is used to substitute erythropoietin in severe anemias due to end stage renal disease or treatment of cancer with cytostatic agents. Side effects include hypertension and increased risk of thrombosis. 

The response to erythropoietin products must be monitored closely to prevent adverse effects associated with these agents. The common adverse effects experienced include hypertension and thrombosis. Concomitant drugs with the same adverse-effect profile may increase a patient s risk for these complications. Also, the patient s overall survival may be decreased if the hemoglobin level is titrated to above the recommended 11 to 12 g/dL (110-120 g/L or 6.82-7.44 mmol/L) value. Therefore, it is important to follow the dosing and titration scheme recommended by the NCCN and summarized in... 

The pathogenesis of hypertension in patients with CKD is multifactorial and includes fluid retention, increased sympathetic activity, an endogenous digitalis-like substance, elevated levels of endothelin-1, erythropoietin use, hyperparathyroidism, and structural arterial changes. 

Toxicity studies traditionally are conducted using normal animals. However, studies in animal disease models may provide additional safety information regarding the possibility of disease exacerbation. For example, the administration of human recombinant erythropoietin was associated with hypertension in patients with chronic renal failure, and also in uraemic dogs, but not in normal dogs. 

Epoetin alfa Agonist of erythropoietin receptors expressed by red cell progenitors Stimulates erythroid proliferation and differentiation, and induces the release of reticulocytes from the bone marrow Treatment of anemia, especially anemia associated with chronic renal failure, HIV infection, cancer, and prematurity prevention of the need for transfusion in patients undergoing certain types of elective surgery IV or SC administration 1-3 times per week Toxicity Hypertension, thrombotic complications, and, very rarely, pure red cell aplasia to reduce the risk of serious CV events, hemoglobin levels should be maintained < 12 g/dL... 

The most common adverse effects of erythropoietin are associated with a rapid increase in hematocrit and hemoglobin and include hypertension and thrombotic complications. These difficulties can be minimized by raising the hematocrit and hemoglobin slowly and by adequately monitoring and treating hypertension. Allergic reactions have been infrequent and mild. 

Several factors contribute to the development of hypertension. One is the loss of the hypoxic vasodilatory response, leading to an increase in peripheral vascular resistance (63), but more important is the rise in blood viscosity, which increases with the hematocrit in both normotensive and hypertensive individuals (64). It is still being debated whether hypertension occurs only in patients with pre-existing hypertension or in normotensive patients as well, but about 30% of all patients require increased or de novo antihypertensive therapy as they respond to erythropoietin treatment (65). 

The adverse effects of erythropoietin in neonates are minimal compared with adults. There were no hypertensive effects reported and no effect on development and growth measured at 18-22 months (111). In a multicenter, randomized, double-blind trial in 21 anemic HIV-infected children, who were concomitantly treated with antiretroviral drugs, epoetin was effective and safe (112). 

Kuriyama S, Tomonari H, Tokudome G, Kaguchi Y, Hayashi H, Kobayashi H, Horiguchi M, Ishikawa M, Hara Y, Hosoya T. Association of angiotensinogen gene polymorphism with erythropoietin-induced hypertension a preliminary report. Hypertens Res 2001 24(5) 501-5. 

Human recombinant erythropoietin (rhEPO or epoetin) is is a synthetic version of human EPO that is used to treat anemia. Following replenished iron stores and exclusion of other causes of anemia, the addition of recombinant epoetin is indicated for the treatment of CKD-related anemia. The gene for human EPO was cloned in 1985 and epoetin was introduced into clinical practice shortly afterwards.It is effective at correcting the anemia of CKD in 90% to 95% of patients. The most common side effect is hypertension and therefore blood pressure should be well controlled before the introduction of treatment. Hypertension may develop or worsen in 23% of patients. Failure to respond to treatment requires thorough investigation for many potential causes (Box 45-2). It is estimated that 3 million patients worldwide have received treatment with epoetin. Pure red cell aplasia (PRCA) has occurred in patients treated with epoetin. This has been described in a small number of patients receiving epoetin via the subcutaneous route. In the majority of cases, neutralizing antibodies to EPO have been detected. If a case of PRCA is proven, then no further recombinant erythropoietin products can be administered. 

Epoetin alpha (e.g., Epogen) Epoetin alpha is recombinant human erythropoietin. Erythropoetin, which is synthesized in the kidney in response to hypoxia or anemia, stimulates erythropoiesis. Epoetin alpha is indicated for anemia in patients with chronic renal failure, because these patients are unable to synthesize erythropoetin to correct the anemia. Additional uses include correcting zidovudine (AZT)-induced anemia in HIV-infected patients and chemotherapy-induced anemia in cancer patients (unlabelled use). Several weeks of therapy are required before the hematocrit levels rise, therefore, this drug cannot replace transfusions for the acute treatment of severe anemia. Epoetin alpha should not be used in patients with uncontrolled hypertension because the elevation in hematocrit may exacerbate hypertension. 

A. Orthostatic hypotension. The most important is to limit use of vasoactive substances. If non-pharmacologic measures are not mough then fludrocortisone should be tried starting with a dose of 0.1 mg at bedtime and increased to 0.4 mg/day [38], Side effects are oedema and recumbent hypertension. Other compounds that have been tested with positive results include Erythropoietin, Octreotide, desmopressin and midodrine. 

The kidneys act to filter toxins out of the blood for excretion in the urine. There are complex mechanisms to recover electrolytes, carbohydrates, and amino acids. The kidney is also an endocrine organ, regulating vitamin D metabolism and signaling red blood cell proliferation through erythropoietin. While each of these unique roles is not specifically tied to an inborn error of metabolism, the kidneys are affected by several disorders and may be the source of chronic complications of disease. Symptoms of chronic kidney disease include osteoporosis, hypertension, anemia, and electrolyte abnormalities with the primary means of therapy being hemodialysis or transplant (Box 4.5). 

Cardiovascular In patients with chronic renal disease who are hemodialysis dependent, hypertension may correlate with truncated erythropoietin receptor mRNA in endothelial progenitor cells [84 ]. 

Recombinant human erythropoietin (r-HuEPO) r-HuEPO, which is effective in correcting anemia in patients with end-stage renal failure and patients with malignancies, induces hypertension or worsens existing hypertension in 20-30% of patients... 

A 43-year-old woman with sickle cell nephropathy and hypertension, who had undergone peritoneal dialysis for 1 year, had been given repeated blood transfusions and erythropoietin, leading to severe iron overload. She was given deferasirox 20 mg/kg/day, and her other medications included allopurinol, amlodipine, atenolol, darbepoetin alfa, folic acid, lanthanum carbonate, lisinopril, and losartan. The... 

Epoetin delta differs from the other erythropoietin derivatives in that it is produced in a human cell line using gene-activation technology. It has been approved in Europe but not in the USA for the treatment of anemia associated with chronic kidney disease. In patients with cancer and anemia who were given epoetin delta, possible treatment-related serious adverse events were hypertension, increased serum creatinine, and peripheral vascular disease [99 ]. There was a correlation with higher doses, suggesting that a dose of 150 lU/kg would be most appropriate to start with for this indication. 

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