About Anemia Before considering a patient with both anemia and CKD, a brief introduction to the processes that

contribute to anemia may be helpful. Anemia is the clinical manifestation of a decrease in circulating red blood cell mass and usually is detected by low blood hemoglobin (Hb) concentration. The cause, treatment, and prognostic significance of anemic disorders vary widely. Causes are distinguished clinically by markers of the magnitude and appropriateness of a marrow response to anemia. Under usual conditions, bone marrow generates approximately 200 billion new cells per day to match the number of senescent cells removed from circulation. The expected compensatory response to anemia is a heightened rate of erythropoiesis. Failure to demonstrate a compensatory response signifies slowed or defective erythropoiesis. Thus, hyperproliferative disorders reflect increased destruction of red blood cells with normal marrow response, whereas hypoproliferative and maturation disorders reflect impaired red blood cell production. The cellular and molecular biology of erythropoiesis has important implications for understanding, evaluating, and treating anemia in patients with CKD. Effective circulating red blood cell mass is controlled by specialized interstitial cells in the kidney cortex that are exquisitely sensitive to small changes in tissue oxygenation. If tissue oxygenation decreases because of anemia or other causes, these cells sense hypoxia and produce erythropoietin. Within erythroid islands, the autonomous unit of erythropoiesis in marrow, receptors on the surface of the earliest red blood cell progenitors, erythroid colony-forming units (CFU-Es), bind erythropoietin. Binding of erythropoietin to erythropoietin receptors salvages CFU-Es and the subsequent earliest erythroblast generations from preprogrammed cell death (apoptosis), thereby permitting cell survival and division and the eventual expansion of erythropoiesis. If successful, these erythropoietin-stimulated events increase the production of reticulocytes, restore normal circulating red blood cell mass, and correct tissue hypoxia.

symptoms: Signs and symptoms vary depending on the cause of your anemia, but may include: Fatigue Pale skin A fast or irregular heartbeat Shortness of breath Chest pain Dizziness Cognitive problems Cold hands and feet Headache

Causes The bone marrow makes fewer red blood cells. Other common causes of anemia include blood loss from hemodialysis and low levels of iron and folic acid. These nutrients from food help young red blood cells make hemoglobin, their main oxygencarrying protein.

Prevention We have used IV iron in addition to EPO in the treatment of the anemia. This regimen is based on studies indicating that the effect of EPO is markedly reduced if IV iron is not added. EPO stimulates the rapid production of erythrocytes in the marrow. If the iron supply is inadequate, the RBCs produced are extruded from the marrow with low levels of hemoglobin. Intravenous iron prevents or overcomes this functional iron deficiency. The oral route of iron administration usually does not supply enough iron to the EPO-stimulated bone marrow to produce the increased amount of Hb needed for the increased number of red blood cells produced. The new IV iron preparations such as iron sucrose and iron gluconate are very safe and have been approved for use all over the world. In contrast iron dextran, which was for years the main IV preparation used, not infrequently causes serious adverse side effects. Treatment: The treatment of the anemia of chronic renal failure has changed dramatically in recent years. Until recently, the principal treatments were transfusion of red blood cells and administration of the hormone testosterone. In 1983, the gene for erythropoietin was isolated, then cloned. Subsequently this led to the mass production of erythropoietin and finally to its use in renal failure patients in 1990 (see Chapter 20). It is administered either intravenously at dialysis or subcutaneously. In anemic patients with chronic renal failure, treatment with erythropoietin is now standard practice and has dramatically reduced the need for blood transfusions. The increase in hematocrit seen with patients treated with erythropoietin has generally resulted in improvement in exercise tolerance and overall sense of well-being. It is important to moniter the iron status of treated patients, as iron deficient patients will not respond appropriately to administration of erythropoietin. Updates: L-Carnitine In the opinion of the Work Group, there is insufficient evidence of efficacy to recommend use of L-carnitine in the management of anemia in patients with CKD. The role of carnitine deficiency in the pathogenesis of the anemia of CKD. L-carnitine, which has been studied primarily when administered IV to HD patients, has been postulated to have beneficial effects on ESA-hyporesponsive anemia. One extremely small trial in which 2 children on HD therapy were administered IV Lcarnitine showed an increase in their Hct by 34% with no change in erythropoietin dose delivered. REFERENCE: http://www.kidney.org/professionals/kdoqi/guidelines_anemia/guide1.htm http://www.mayoclinic.com/health/anemia/DS00321/DSECTION=symptoms http://eurjhf.oxfordjournals.org/content/4/6/681.full

http://msl1.mit.edu/ESD10/kidneys/HndbkHTML/ch19.htm http://www.kidney.org/professionals/KDOQI/guidelines_anemia/ped33.htm