Kidney disease, chronic erythropoietin

Anemia of chronic kidney disease A decline in red blood cell production caused by a decrease in erythropoietin production by the progenitor cells of the kidney. As kidney function declines in chronic kidney disease, erythropoietin production also declines, resulting in decreased red blood cell production. Other contributing factors include iron deficiency and decreased red blood cell lifespan, caused by uremia. 

Iron deficiency anemia is treated with oral or parenteral iron preparations. Oral iron corrects the anemia just as rapidly and completely as parenteral iron in most cases if iron absorption from the gastrointestinal tract is normal. An exception is the high requirement for iron of patients with advanced chronic kidney disease who are undergoing hemodialysis and treatment with erythropoietin for these patients, parenteral iron administration is preferred. 

Allergic reactions to ESAs have been infrequent. There have been a small number of cases of pure red cell aplasia (PRCA) accompanied by neutralizing antibodies to erythropoietin. PRCA was most commonly seen in dialysis patients treated subcutaneously for a long period with a particular form of epoetin alfa (Eprex with a polysorbate 80 stabilizer rather than human serum albumin) that is not available in the USA. After regulatory agencies required that Eprex be administered intravenously rather than subcutaneously, the rate of ESA-associated PRCA diminished. However, rare cases have still been seen with all ESAs administered subcutaneously for long periods to patients with chronic kidney disease. 

Ca X P calcium phosphorus product serum calcium multiplied by serum phosphorus CKD chronic kidney disease CPK creatine phosphokinase DEO deferoxamine EPO erythropoietin ESKD end-stage kidney disease ESRD end-stage renal disease FEk fractional excretion of potassium FEn fractional excretion of sodium GFR glomerular filtration rate Hct hematocrit HDL high-density fipoprotein Hgb hemoglobin... 

Patients with anemia secondary to chronic kidney disease are ideal candidates for epoetin alfa therapy. The response in predialysis, peritoneal dialysis, and hemodialysis patients is dependent on the severity of renal failure, erythropoietin dose and route of administration, and iron availability. The subcutaneous route of administration is preferred to the intravenous route because absorption is slower and the amount of drug required is reduced by 20 to 40%. 

Recombinant erythropoietin therapy, in conjunction with adequate iron intake, can be highly ejfective in a number of anemias, especially those associated with a poor erythropoietic response. There is a clear dose-response relationship between the epoetin alfa dose and the rise in hematocrit in anephric patients. Epoetin alfa is effective in the treatment of anemias associated with surgery, AIDS, cancer chemotherapy, prematurity, and certain chronic inflammatory conditions. Darbepoetin alfa also is approved for use in patients with anemia associated with chronic kidney disease and is under review for several other indications. 

The client diagnosed with chronic kidney disease is prescribed erythropoietin (Procrit). Which intervention should the nurse implement Select all that apply. 1. 

Methoxy-PEG-epoetin a (Mircera) Roche (2007) Erythropoietin 30kDaPEG Anemia associated with chronic kidney disease... 

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). 

Erythrocyte-stimulating agents Erjdhrocyte-stimulating agents such as erythropoietin increase BP in as many as 20% of patients with anemia or chronic kidney disease... 

Anemia Treatments. Anemia is an independent predictor of mortality in chronic kidney disease patients and is also associated with worsening of cardiovascular morbidity and accelerated rate of kidney damage. The administration of recombinant human erythropoietin (rHuEpo) has greatly reduced anemia in patients with chronic kidney disease. 

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. 

Port RE, Mehls O. Erythropoietin dosing in children with chronic kidney disease based on body size or on hemoglobin deficit Pediatr Nephrol 2009 24(3) 435-7. 

Bennett CL, Spiegel DM, Macdougall IC, Norris L, Qureshi ZP, Sartor O, et al. A review of safety, efficacy, and utilization of erythropoietin, darbepoetin, and peginesatide for patients with cancer or chronic kidney disease a report from the Southern Network on Adverse Reactions (SONAR). Semin Thromb Hemost 2012 38(8) 783-96. 

An example of the use of activated mPEG-butyric acid 19a includes the PEGylation of erythropoietin P [99]. This conjugate, commercially available as Mircera, is used for the treatment of anaemia associated with chronic kidney disease. 

Molidustat (BAY 85-3934) is a novel inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase (PH), which stimulates erythropoietin (EPO) production and the formation of red blood cells. Phase I data have shown that inhibition of HIF-PH by Molidustat results in an increase in endogenous production of EPO [136]. Molidustat is currently under clinical trials at Bayer for the treatment of patients suffering from renal anemia due to chronic kidney disease. 

Patients with CKD suffer from a decrease in erythropoietin production because erythropoietin is produced mainly in the kidneys.4,5 Finally, in patients with anemia of chronic disease, there is a blunted erythropoietin production as well as a diminished response to erythropoietin.9 Anemia of chronic disease also affects iron homeostasis, causing iron sequestration into storage sites and decreasing the amount available to the rest of the body.9... 

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. 

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. 

Erythropoietin stimulates erythroid proliferation and differentiation by interacting with specific erythropoietin receptors on red cell progenitors. It also induces release of reticulocytes from the bone marrow. Endogenous erythropoietin is produced by the kidney in response to tissue hypoxia. When anemia occurs, more erythropoietin is produced by the kidney, signaling the bone marrow to produce more red blood cells. This results in correction of the anemia provided that bone marrow response is not impaired by red cell nutritional deficiency (especially iron deficiency), primary bone marrow disorders (see below), or bone marrow suppression from drugs or chronic diseases. 

Erythropoietin is a glycoprotein hormone encoded by a gene on the long arm of chromosome 7 (7q) and 90% is produced in the kidney (the remainder in the liver and other sites) in response to hypoxia. The anaemia of chronic renal failure is largely due to failure of the diseased kidneys to make enough erythropoietin. The principal action of the hormone is to stimulate the proliferation, survival and differentiation of erythrocyte precursors. The manufacture of erythropoietin for clinical use became possible when the human gene was successfully inserted into cultured hamster ovary cells. 

Revicki DA, Brown RE, Feeny DH, Henry D, Teehan BP, Rudnick MR, et al. Health-related quality of life associated with recombinant human erythropoietin therapy for predialysis chronic renal disease patients. Am J Kidney Dis 1995 25 548-54. 

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. 

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