Renal erythropoietin production

Delayed blood regeneration due to inadequate renal erythropoietin production... 

Carboxyhemoglobinaemia Chronic obstructive airways disease Pulmonary hypoventilation syndrome Right-to-left cardiac shunt Absolute - physiologically inappropriate Ectopic erythropoietin production Renal carcinoma and cysts Hepatoma... 

Therapy in those with ectopic erythropoietin production depends upon correcting the hormone level by removing whatever tissue is responsible for its production and examples include nephrectomy for renal carcinoma or the classical, albeit rare, cerebellar haemangioblastoma. Where metastases have occurred appropriate cytotoxic chemotherapy is needed and response in haematocrit becomes a rough indicator of the success with which the tumour is responding to therapy. In some individuals venesections are necessary to control the raised haemoglobin. 

Abnormalities of liver function tests are occasionally seen, as is a varying degree of anemia due to reduced erythropoietin production by damaged renal tubular cells. After intrathecal therapy with amphotericin, seizures and a chemical arachnoiditis may develop, often with serious neurologic sequelae. 

Stockelman et al. (1998) described chronic renal failure in a mouse model of human adenine phospho-ribo-syltransferase deficiency. Hamilton and Cotes (1994) used a partial nephrectomy model in mice with two-thirds of the total renal mass excised to evaluate erythropoiesis and erythropoietin production from extrarenal sources such as the submandibulary salivary gland. Koumegawa et al. (1991) suggested the DBA/2FG-pcy mouse, which develops numerous cysts in kidney cortex and medulla, a progressive anemia and an elevation of blood urea nitrogen, as a useful spontaneous model of progressive renal failure. 

Worldwide, 112 cases of pure red cell aplasia have been reported after subcutaneous administration of epoetin alfa (especially Eprex) in patients with chronic renal insufficiency. In these patients, neutralizing anti-eiythropoietin antibodies were detected (82-84) these antibodies cross-react with all other erythropoietin products. This adverse... 

Polycythemia is characterized by an increase in the number, and in the hemoglobin content, of circulating red cells. In patients who have chronic anoxia from impaired pulmonary ventilation or congenital or acquired heart disease, the increase in plasma erythropoietin leads to secondary polycythemia. Some renal cell carcinomas, hepatocarcinomas, and other tumors, which produce physiologically inappropriate amounts of erythropoietin, may also cause secondary polycythemia. Conversely, anemia can result from renal insufficiency and from chronic disorders that depress erythropoietin production. In polycythemia vera (primary polycythemia), which is a malignancy of erythrocyte stem cells of unknown cause, erythropoietin levels are normal or depressed. 

Most patients who require dialysis have a normocytic normochronic anemia and a hypoproliferative bone marrow. As erythropoiesis decreases with advancing renal disease, iron shifts from circulating red cells to the reticuloendothelial system, leading to high serum ferritin levels. Repeated blood transfusion is also a common cause of iron overload and hyperferritinemia. Clearly the most important cause of the anemia of chronic renal failure is decreased erythropoietin production by the kidneys uremic patients have much lower plasma erythropoietin levels than comparably anemic patients with normal renal function (E8). Less important causes are shortened red cell survival, iron or folate deficiency, aluminum intoxication, and osteitis fibrosa cystica (E8). Uremic retention products such as methylguanidine (G10) and spermidine (R2) may also have an adverse effect on erythropoiesis. 

Nomiul erj lhnipoiesis requires iron, viiumin nnil folic acid. A deficiency of any of these causes anaemia. Erythropoietic activity is regulated by erythix oietiii. a hormone released mainly by the kidneys. In chronic renal failure, anaemia often occurs because of a I all in erythropoietin production. 

Anemia may occur in patients with chronic renal failure as tlie result of the inability of the kidney to produce erythropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia Two examples of drug used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp). 

The progenitor cells of the kidney produce 90% of the hormone erythropoietin (EPO), which stimulates red blood cell (RBC) production. Reduction in nephron mass decreases renal production of EPO, which is the primary cause of anemia in patients with CKD. The development of anemia of CKD results in decreased oxygen delivery and utilization, leading to increased cardiac output and left ventricular hypertrophy (LVH), which increase the cardiovascular risk and mortality in patients with CKD. 

Although the kidneys are not considered endocrine glands per se, they are involved in hormone production. Erythropoietin is a peptide hormone that stimulates red blood cell production in bone marrow. Its primary source is the kidneys. Erythropoietin is secreted in response to renal hypoxia. Chronic renal disease may impair the secretion of erythropoietin, leading to development of anemia. The kidneys also produce enzymes. The enzyme renin is part of the renin-angiotensin-aldosterone system. As will be discussed, these substances play an important role in the regulation of plasma volume and therefore blood pressure. Other renal enzymes are needed for the conversion of vitamin D into its active form, 1,25-d i hyd ro xyv itamin D3, which is involved with calcium balance. 

PD Patients with chronic renal failure (CRF) and those receiving chemotherapy developed anemia due to deficiency in erythropoietin. Aranesp stimulates the production of red blood cells (RBCs). It mimics the natural... 

Mechanism of Action An anabolic steroid that promotes tissue-building processes, increases production of erythropoietin, causes protein anabolism, and increases hemoglobin and red blood cell volume. Therapeutic Effect Controls metastatic breast cancer and helps manage anemia of renal insufficiency. 

Clinical pharmacology Erythropoietin is instrumental in the production of red cells from the erythroid tissues in the bone marrow. The majority of this hormone is produced in the kidney in response to hypoxia, with an additional 10% to 15% of synthesis occurring in the hver. Erythropoietin functions as a growth factor, stimulating the mitotic activity of the erythroid progenitor cells and early precursor cells. Chronic renal failure patients often manifest the sequelae of renal dysfunction, including anemia. Anemia in cancer patients may be related to the disease itself or the effect of concomitantly administered chemotherapeutic agents. 

Epoetin alfa, recombinant erythropoietin, is a glycoprotein that simulates erythrocyte production. Epoetin alfa is administered three times weekly subcutaneously or intravenously. Epoetin is used to treat anemia in patients with chronic renal failure, HIV infection, and patients receiving chemotherapy [104]. Development of a safe, effective nasal formulation of epoetin alfa, containing an absorption enhancer could once again improve the efficacy of epoetin alfa therapy, and reduce the number of injections required in these sensitive patient populations. 

Anemia. Testosterone and similar compounds are potent stimulators of erythropoietin synthesis from the kidneys and other tissues.109 Erythropoietin, in turn, stimulates production of red blood cell synthesis in bone marrow. Human erythropoietin, however, can now be synthesized using recombinant DNA techniques. Hence, various types of anemia that occur secondary to renal disease, cancer chemotherapy, and so forth are usually treated directly with recombinant erythropoietin.109 Nonetheless, androgens may be used as an adjunct to erythropoietin and other drugs to stimulate red blood cell production in certain patients with severe or recalcitrant anemia.10... 

In anaemia of chronic disease, anaemia associated with chemotherapy or anaemia associated with renal disease, recombinant erythropoietin can stimulate red cell production. 

Human erythropoietin (hEpo) is a glycoprotein of 36,000 daltons, produced by the kidney in response to hypoxia. It regulates the rate of production of mature erythrocytes by stimulating the proliferation and differentiation of erythroid precursor cells. Renal failure leads to lack of this growth factor which, in turn, leads to anemia (Hillman, 1990 Cotes and Spivak, 1991). 

Figure 18.2 illustrates a graded dose-effect relationship for recombinant human erythropoietin (rhEPO) in patients with end-stage renal disease (2). Erythropoietin/ which is produced by the kidney in response to hypoxia/ is a naturally occurring hematopoietic growth factor that stimulates bone marrow production... 

With progressing renal failure, the kidney loses its ability to excrete acid into the urine. The result is acidosis. Acidosis can be treated with sodium bicarbonate or sodium citrate (Brermer and Larazus, 1994). The kidney performs several functions not directly related with urine production, and these include the synthesis of calcitriol (the active form of vitamin D) and erythropoietin (a hormone that stimulates red blood cell production). Thus, treatment of chronic renal failure may include injections of calcitriol and erythropoietin. 

Epogen Procrit ) - more fully termed 1-165-erythropoetin (human clone y HEPOFL13 protein moiety -is recombinant human erythropoietin produced by genetically engineered Chinese hamster cells. It is a haematinic and regulates red blood cell production. It is used as a haemopoietic and ANTMNAEMIC in the treatment of anaemia associated with chfbnic renal failure, and also in ANTICANCER chemotherapy to stimulate erythrocyte production after treatment. 

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