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Article Excerpt
Anemia treatment has always been a major focus in the management of dialysis patients. The advent of the recombinant human erythropoietin (rHuEPO) era did not change that; it did, however, shift the main cause of anemia from erythropoietin insufficiency to iron deficiency. Instead of multiple transfusions and iron overload, now rHuEPO is the mainstay of anemia treatment, and iron deficiency is a pervasive problem.
Iron deficiency must be aggressively addressed to achieve optimal patient outcomes. Most patients are iron deficient when they start hemodialysis, and despite increasing recognition of this condition, iron deficiency remains present in more than 50% of hemodialysis patients receiving rHuEPO (NKF, 2001).
Causes of Iron Deficiency
The cause of iron deficiency in dialysis patients is multifactorial. There are two kinds of iron deficiency: absolute iron deficiency denotes an insufficient total body store, whereas functional iron deficiency involves a relative inaccessibility of otherwise adequate total body iron stores. End stage renal disease (ESRD) patients are prone to both types of iron deficiency.
Causes of absolute iron deficiency may include malabsorption (Goch, Birgegard, Danielson, & Wikstrom, 1996; Kooistra et al., 1998), blood loss from frequent laboratory testing (weekly, bi-weekly, and monthly labs) (Fishbane & Maesaka, 1997), lowgrade gastrointestinal bleeding (Akmal, Sawelson, Karubian, & Gadallah, 1994), and hemolysis (Yee & Besarab, 2002). These contributing factors are common to all chronic kidney disease and ESRD patients. However, in hemodialysis patients, accidental blood loss from the vascular access, frequent surgical procedures, and blood loss from blood left in the extracorporeal circuit (i.e., blood lines and dialyzer) are primarily responsible for absolute iron deficiency (Fishbane & Maesaka, 1997). It is the magnitude of these blood losses, estimated to be up to 3 g per year, that make oral iron repletion particularly impractical in this patient population (Cook & Eschbach, 1975).
Even with adequate iron stores, which most dialysis patients lack, available iron may be insufficient to meet the demand caused by rHuEPO. This situation is termed fractional iron deficiency. Simple infection and inflammation, associated with ESRD, can increase synthesis of the iron storage protein, ferritin, resulting in the sequestration of iron in the reticuloendothelial system (RES) (Yee & Besarab, 2002). Anemia and inflammation-induced cytokine production can interfere with both the effect of erythropoietin on the bone marrow and release of stored iron from the RES (Goicoechea et al., 1998; Silverberg, Iaina, Wexler, & Blum, 2001; Yee & Besarab, 2002). Even without this "RES blockade," during rHuEPO therapy, a superphysiologic rate of erythropoiesis can cause iron demand to exceed supply. Functional iron deficiency may occur in 40% to 60% of rHuEPO-treated dialysis patients.
Consequences of Iron Deficiency
The result of iron deficiency is that the effect of rHuEPO is blunted (Adamson, 1994; Macdougall, Chandler, Elston, & Harchowal, 1999; Richardson, Bartlett, & Will, 2001; Taylor, Peat, Porter, & Morgan, 1996), with, at a minimum, an increased cost of rHuEPO estimated at $109 to $240 per patient per month (Besarab et al., 2000; Macdougall et al., 1999), and, at worst, persistent anemia. Anemia impairs activities of daily living (ADL), rehabilitation, quality of life, cognitive function, nutrition, and energy (Delano, 1989; Tong & Nissenson, 2001). Anemia reduces cardiac function and increases hospitalization and mortality (Levin, Singer, Thompson, Ross, & Lewis, 1996; Silverberg et al., 2001; Tong & Nissenson, 2001). Silverberg recently described the "Cardio renal anemia syndrome" in which anemia exacerbates chronic heart failure (CHF), accelerating renal deterioration, and in turn further worsening anemia (Silverberg et al., 2003). This necessitates a treatment plan that addresses the individual elements as a unit, all of which must be treated concurrently.
IV Iron Therapy
The considerations discussed above...
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