**4. Evolving concept of iron as an adjuvant of erythropoiesis —Stimulating agent therapy over the last two decades**

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 drugs [1, 9].

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 parenteral iron products [7, 10, 26].
