**1. Introduction**

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56 Updates in Hemodialysis

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During the past two decades, routine use of recombinant erythropoeisis-stimulating agents (ESA) has enabled anemia to be corrected in most patients with end-stage renal disease, permitting better outcomes and improving quality of life [1]. The use of ESA is frequently associated with iron deficiency, resulting primarily from massive transfer of stored iron to erythroid progenitor cells [2]. Mobilization of iron from repleted storage sites may also be inadequate, resulting in functional iron deficiency [3]. Moreover, blood loss related to hemo‐ dialysis itself and to occult intestinal bleeding due to uremic enteropathy can markedly aggravate iron deficiency in this setting [1]. As successful use of ESA requires sufficient available iron before and during therapy, almost all dialysis patients on ESA currently receive parenteral iron therapy [3]. The dual risk of iron deficiency and iron overload must therefore be closely monitored in dialysis patients. Interestingly, most relevant studies published in the last two decades have focused chiefly on the detection and treatment of iron deficiency in dialysis patients, while very few have examined iron overload [3-4].

Until recently it was widely considered that iron overload among dialysis patients was more prevalent during the pre-ESA era, when blood transfusion was frequently used to treat anemia and when intravenous iron therapy was given without concomitant ESA administration; iron overload was therefore considered rare, or even exceptional, among dialysis patients in the ESA era but is now an increasingly recognized clinical situation [3-7].

The only laboratory parameter available to screen for iron overload in dialysis patients is serum ferritin, but confirmation necessitates liver or bone biopsy, and few data were available on patients with end-stage renal disease until now, owing to the aggressiveness of these histo‐ logical examinations [4]. Moreover, serum ferritin is an acute-phase reactant, and these patients' frequent systemic inflammation may inhibit both iron mobilization from reticuloen‐

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dothelial stores and intestinal iron absorption via hepcidin modulation; the relationship between ferritin and iron stores may therefore be blunted or skewed [4, 8].

American and European clinical practice guidelines (KDOQI-2006 and European Best Practice Guideline-2009) warned against regular iron administration when the ferritin concentration exceeds 500 µg/L, although the former guideline allowed clinicians to make a decision on IV iron administration above this level after carefully weighing up ESA responsiveness, hemo‐ globin and transferrin saturation, and the patient's clinical status [1, 9]. It is also worthy of note that the recent KDIGO-2012 guideline proposed a trial of IV iron in dialysis patients prior to ESA use, with the aims of sparing these expensive drugs and of reaching high TSAT (30%) and ferritin (500 µg/L) target values [10]; however, these new KDIGO target values for iron biomarkers were not fully endorsed by EDTA-ERA because of the potential risk of iron overload [11]. Likewise, the Japanese Society for Dialysis recently proposed that a minimal amount of IV iron (up to 650 mg in the induction phase) should be given to dialysis patients, and only in case of true iron deficiency (ferritin <100 µg/L), while also warning against maintenance intravenous iron therapy because of the risk of iron toxicity [12].
