Different Oral Iron Dosing Regimens in Treatment of Iron Deficency Anemia in Patients With Chronic Kidney Disease

Anemia is common in chronic kidney disease (CKD) and has been associated with impaired quality of life, cardiovascular disease (CVD) and mortality. Iron deficiency is common in patients with CKD and an important modifiable factor in treatment of anemia. In particular, the Kidney Disease: Improving Global Outcomes (KDIGO) anemia work group guidelines define anemia in CKD as a hemoglobin concentration of \<13.0 g/dL in men and \<12.0 g/dL in women. The current guidelines recommend trial of iron supplementation in CKD when increase in hemoglobin concentration or decrease in erythropoietin dose is desired and investigations reveal percentage transferrin saturation (%TSAT) ≤ 30% and serum ferritin ≤ 500 ng/ml. The absorption of iron from gastro-intestinal tract and release of iron from reticuloendothelial cells for erythropoiesis are tightly regulated through hepcidin-ferroportin axis. Hepcidin concentrations increase in response to iron excess and inflammation. CKD is associated with elevated hepcidin and ferritin concentrations due to underlying inflammation, independent of iron status. Iron-deficiency anemia in individuals with CKD may result from functional iron deficiency, absolute iron deficiency, or both. The factors contributing to functional iron deficiency are chronic inflammation and poor hepcidin clearance seen in CKD, whereas absolute iron deficiency includes poor gastrointestinal (GI) dietary iron absorption and blood loss. In patients with CKD who are not on dialysis, oral route may be preferred as initial mode of iron supplementation. Oral iron is inexpensive, self-administered, convenient and easily available. Three different oral iron supplement strategies-once daily, multidose per day, and alternate-day dose-improve hemoglobin (Hgb) and iron indices in patients with iron deficiency anemia and chronic kidney disease (CKD). Study showed that daily doses of oral iron reduced its absorption by increasing serum hepcidin levels. This study also found that administration of oral iron on alternate days as single doses improved iron absorption. Theoretically, using lower doses and increasing time interval between consecutive doses might reduce the amount of unabsorbed iron in the gastrointestinal tract resulting in lesser gastrointestinal side effects. However, the major concern with alternate day dosing is that only half the total amount of iron is supplemented per unit time compared to daily dosing. More recent data suggest that lower doses and infrequent administration may be as effective as the traditional regimen while probably associated with lower rates of adverse effects. Investigators will investigate the effect of every other day, once daily and three times a day dosing of oral iron formulation on measures of iron sufficiency in patients with stages 2,3 and 4 CKD through a randomized controlled trial.