**5. Increased use of IV iron in dialysis patients worldwide in the last two decades**

A recent epidemiological analysis of the management of anemia in hemodialysis patients in the USA, based on USRDS data, showed an increase in the use of IV iron from 64% of patients in 2002 to 76% in 2008, together with an increase in the infused dose from 166 mg/month to 216 mg/month [27]. In addition, during the first year of hemodialysis, the usual monthly infused dose of iron was shown to be far higher, ranging from 270 mg to 305 mg [27]. The change made to the ESA label by the Food and Drug Administration in June 2010 also led to an increase in the percentage of US patients receiving IV iron, from 57% (August 2010) to 71% (August 2011), together with a significant decline in the ESA dosage and an increase in the median ferritin level from 556 to 650 µg/L, with values exceeding 800 µg/L in 34% of patients [28]. While the median dose of IV iron remained largely stable at 190 mg/month, it is note‐ worthy that 18% of patients received more than 500 mg/month during this period [28].

increased by antiplatelet and antivitamin K drugs: dialysis patients thus treated require higher IV iron dosages to replenish their iron stores (e.g 703 to 961 mg/year) [22, 23]. Thus, total blood losses in a hemodialysis patient with a native arteriovenous fistulae treated in a non academic center and not receiving antiplatelet or antivitamin K drugs can be estimated at 2.85 L/year (1.425 g of iron/year), whereas a patient with the same clinical profile but a double-lumen tunnelized catheter will lose 5.5 L/year (2.765 g of iron); note that both values are far lower

**4. Evolving concept of iron as an adjuvant of erythropoiesis —Stimulating**

With the advent of erythropoietin replacement therapy in the eighties, the goal of iron therapy was to maintain iron stores and thereby prevent true iron deficiency, mainly with oral iron supplements when the serum ferritin level was less than 50 µg/L; IV iron was advocated at that time as a second-line option in case of severe iron deficiency, poor tolerance or inefficacy of oral iron salts [24, 25]. Parenteral iron therapy has gained popularity in the nephrology community in the last fifteen years because of its convenience (infusion during dialysis sessions), its superiority over oral preparations for treating true iron deficiency, and its ability to overcome functional iron deficiency, a very common clinical situation in hemodialysis patients; in addition, this treatment enabled cost savings of about 20%-30% on expensive ESA

Based solely on bone marrow studies and the lack of known long-term adverse effects, recent guidelines have redefined iron deficiency and adjusted iron-store repletion criteria to even higher levels (the KDIGO 2012 target for "upper normal" ferritin in hemodialysis patients is now 500 µg/L), underlining the risk of functional iron deficiency during ESA treatment and the ability of IV iron to spare ESA use, and even going so far as to advo‐ cate a trial of IV iron prior to ESA initiation. All these changes have amplified the use of

**5. Increased use of IV iron in dialysis patients worldwide in the last two**

A recent epidemiological analysis of the management of anemia in hemodialysis patients in the USA, based on USRDS data, showed an increase in the use of IV iron from 64% of patients in 2002 to 76% in 2008, together with an increase in the infused dose from 166 mg/month to 216 mg/month [27]. In addition, during the first year of hemodialysis, the usual monthly infused dose of iron was shown to be far higher, ranging from 270 mg to 305 mg [27]. The change made to the ESA label by the Food and Drug Administration in June 2010 also led to an increase in the percentage of US patients receiving IV iron, from 57% (August 2010) to 71% (August 2011), together with a significant decline in the ESA dosage and an increase in the

than the classical estimates of 2 to 6 g/year [20].

**agent therapy over the last two decades**

drugs [1, 9].

60 Updates in Hemodialysis

**decades**

parenteral iron products [7, 10, 26].

Very similar trends in the use of IV iron were recently observed in other industrialised countries, with the exception of Japan: the percentage of patients treated with IV iron rose between 1999 and 2010 from 50% to 71% overall, from 65% to 80% in Canada, from 55% to 70% in France, from 65% to 80% in Germany, and from 60% to 80% in the UK; during the same period (1999-2010), the mean ferritin level rose from 380 to 450 µg/L in Canada, from 420 to 580 µg/L in Germany and from 400 to 500 µg/L in the UK, while it remained stable in France at around 400 µg/L [29]. In Japan, the percentage of patients receiving IV iron rose only from 25% to 36% and the mean ferritin level rose only from 280 to 320 µg/L [29]. The overall mean monthly iron dose administered in industrialized countries other than the U.S. rose by 21%, from 232 mg/month in 1992 to 281 mg/month in 2010 [29].
