**3. Anemia in chronic kidney disease**

In a prospective trial by Stoves et.al, PO vs IV route of iron administration was studied. Forty five anemic patients with CKD, not on dialysis, were randomized to receive oral (ferrous sulfate 200 mg tid) or intravenous (300 mg iron sucrose monthly) iron therapy. EPO was started at the same time and the dose adjusted according to a pre-established protocol. After an average follow up of 5.2 months, there were no significant differences in Hb response and EPO dose between the two groups.**13** A prospective study by Charytan et. al. in 96 CKD anemic patients on EPO compared the efficacy of IV iron (5 doses of 200 mg iron sucrose weekly) to oral iron (ferrous sulfate 325 mg tid). They found an increase in Hb and ferritin following IV iron, whereas the oral iron group demonstrated an increase in Hb without increase in iron stores.**14** Both of the above studies failed to show IV iron superior to PO in either selected group of CKD patients. Van Wyck et.al. conducted a larger study of 182 non dialysis-dependent CKD (stages 3 to 5) patients to compare oral iron vs. IV iron. That randomized, controlled, multicenter trial tested IV iron as sucrose 1 g in divided doses over 14 days vs oral ferrous sulfate 325 mg three times a day for 56 days. Inclusion criteria for the group were Hb ≤11 g/dL, TSAT ≤25%, and ferritin ≤300ng/mL. EPO/DPO dose was not changed for eight weeks prior to or during the study. The proportion of patients achieving the primary outcome (Hb increase ≥1 g/dL) was greater in the IV iron treatment group than in the oral iron treatment group (44.3% vs. 28.0%, P = 0.0344), as was the mean increase in Hb by day 42 (0.7 vs. 0.4 g/dL, P = 0.0298).**<sup>15</sup>** Agarwal and colleagues conducted a randomized, multicenter, controlled trial in 75 adult, anemic, iron-deficient, non-dialysis CKD patients not receiving ESAs. The patients were randomly assigned to receive either IV ferric gluconate 250 mg weekly for 4 weeks or oral ferrous sulfate 325 mg three times a day for 42 days. Both oral and IV iron similarly increased Hb in anemic CKD patients not receiving ESAs.**16** 

A new IV iron preparation, ferumoxytol has been approved in the United States. It appears to be safe and effective when given as a rapid infusion of up to 510 mg in patients with CKD and patients on dialysis. A Phase III trial randomly assigned 304 patients with CKD in a 3:1 ratio to two 510-mg doses of intravenous ferumoxytol within 5 ± 3 days or 200 mg of elemental oral iron daily for 21 days. Among patients who were not receiving ESAs, Hb increased 0.62 ± 1.02 g/dL with ferumoxytol vs. 0.13±0.93 g/dL with oral iron. Among patients who were receiving ESAs, Hb increased 1.16±1.49 g/dL with ferumoxytol vs. 0.19±1.14 g/dL with oral iron. The increase in Hb at day 35, the primary efficacy end point, was 0.82+/-1.24 g/dL with ferumoxytol and 0.16+/-1.02 g/dL with oral iron (P<0.0001).**17** The authors concluded that a regimen of two doses of 510 mg of intravenous ferumoxytol administered rapidly within 5±3 days was well tolerated and had the intended therapeutic effect. The side effects associated with IV iron in the abovementioned studies were headache, myalgia, and hypotension (particularly in thin, older women<65 kg). Intravenous iron sucrose has shown better tolerability. Oral iron has more GI associated side effects including constipation, diarrhea, nausea and vomiting.**13-17**

As a result of these studies the K/DOQI guidelines have recommended that either oral iron therapy or intravenous iron therapy can be given in CKD patients.
