NN&I - April 2010
Patient Management 30 Nephrology News & Issues April 2010www.nephronline.com roid marrow has a continuous supply of iron necessary to incorporate Hb into developing erythrocytes. In addi -tion, regular, low-dose regimens may reduce the risk of Hb cycling, in which hemodialysis patients experience fluc -tuations in Hb levels both above and below the target ranges. More than 90% of patients on hemodialysis have been shown to experience Hb cycling.18 Hb cycling is a recognized consequence of poorly designed ESA dosing strategies, in which ESAs are delivered at high doses (resulting in overshooting of Hb targets) and then withheld for extended periods (resulting in dramatic reduc -tions in Hb levels).19-22 It also has been shown that poorly designed IV iron dosing strategies can contribute to Hb cycling.18,22 A well-designed IV iron and ESA dosing strategy is an important consid -eration in anemia management, given that fluctuations in Hb levels have been associated with adverse patient out -comes.20,21 For example, in a six-month study of 152,846 Medicare hemodialysis patients, those who experienced high- amplitude fluctuations in their Hb lev-els had much higher rates of hospital admissions and admissions for infec -tions, and a longer length of hospital stay, than those who maintained a tar -get Hb level of 11 to 12.5 g/dL over the entire six months.21 Although longer-term studies are needed, several short -er-term studies show that giving IV iron in regular, low-dose regimens can maintain Hb and iron indexes within target ranges, as well as reduce ESA requirements.23-26 The fact that IV iron effectively reduc-es ESA requirements is important, given that a significant percentage of patients fail to respond to even high doses of ESAs with a corresponding increase in Hb or Hct. This condition is called "ESA hyporesponsiveness." Several fac -tors have been implicated in ESA hypo -responsiveness, including inflamma -tion, infection, inadequate dialysis, alu -minum overload, vitamin B12 or folic acid deficiency, and oxidative stress. However, the most important cause is iron deficiency, whether absolute or due to iron-restricted erythropoiesis (i.e., functional iron deficiency).27 In one of the largest studies looking at inadequate response to ESAs, encom-passing more than 38,000 hemodialysis patients who received ESAs for at least three consecutive calendar quarters, the most important predictors of ESA hyporesponsiveness were markers of iron deficiency, including serum ferritin <200 ng/mL and TSAT <20%.12Correspondingly, the greatest level of ESA response was seen with serum ferritin of 500 to 1,200 ng/mL and TSAT >30% (see Figure 2).12 Consistent with these findings, our study showed an ESA dose reduction of approximately 19% over the course of one year when a serum ferritin cutoff of 1,200 was used in conjunction with regular, low doses of IV ferric gluconate. DRIVE, as well as numerous other studies, have-shown that IV iron use can result in dramatic improvements in response to ESAs.2,6,23,24,26,28,29The ability to reduce ESA usage is a Figure 2A. The greatest level of ESA response was observed with serum ferritin of 500 to 1,200 ng/mL and TSAT >30%. Reprinted with permission from Kalantar-Zadeh, 2009.12 Unadjusted Case Mix e ss st Responsiv en e g to ESA s pondin g o of Re s d ds Rat i O d Worst Responsivenes s Greatest ResponsivenessSerum Ferritin, ng/mL 1.5 08 1 0 . 8 0.6 <200 200-499 500-799 800-1200 \0371200Figure 2A Unadjusted Case Mix e ss st Responsiv en e g to ESA s pondin g o of Re s d ds Rat i O d Worst Responsivenes s Greatest ResponsivenessSerum Ferritin, ng/mL 1.5 08 1 0 . 8 0.6 <200 200-499 500-799 800-1200 \0371200Figure 2A Patient Management_0410_7.indd 30 3/18/10 3:46:33 PM
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