Iron supplementation is crucial for the treatment of anemia of CKD. Iron supplementation is administered either orally or intravenously. Although intravenous (IV) iron is preferred for patients with CKD receiving dialysis (CKD stage 5D), the method of iron replacement for patients with CKD stages 3 to 5 is controversial.

Oral iron is widely available and is inexpensive. However, oral iron therapy imposes a high pill burden on patients. Both the high pill burden and unpleasant side effects associated with oral iron therapy can lead to adherence issues that may ultimately limit efficacy as well as patient quality-of-life (QoL). It should also be considered that uremia is associated with reduced gastrointestinal absorption of iron, while chronic inflammation and medication interactions (notably, calcium carbonate, which is used by many patients with CKD as a phosphate binder) can also impair gastrointestinal iron uptake, thereby further hampering the efficacy issues.

Oral iron is less costly and easier to administer, but IV iron allows larger doses of iron to be administered rapidly and is better tolerated by most patients. Compared to oral iron, IV iron better achieves a repletion of Iron stores, which decreases the need for blood transfusions and improves QoL for many patients with CKD.

Concerns regarding IV iron therapy include anaphylaxis, bacterial infections and atherosclerosis promotion. The PIVOTAL study suggested, the proactive use of high-dose IV iron can reduce the amount of erythropoiesis-stimulating agent needed to treat anemia in dialysis patients with no short-term increase in the risk for vascular complications or infections.

A recent meta-analysis including 24 trials, 13 including 2,369 patients with CKD stages 3 to 5 and 11 including 818 patients with CKD stage 5D showed that IV iron is the preferred treatment for both patients with CKD stage 5D and those with CKD stages 3 to 5.

In nondialyzed CKD, subjects intolerant or nonresponsive to oral iron therapy, can be effectively treated with novel IV iron preparations, such as iron carboxymaltose, that allow a complete and rapid correction of iron deficient anemia. Furthermore, this iron compound is associated with lower rate of adverse effects since the carbohydrate shell (carboxymaltose) is more stable than gluconate and saccharate thus reducing the release of free iron in the bloodstream.

Of note, the possibility of administering this drug at high doses and reduced frequency decreases the risk of infusion reactions. Finally, a substantial economic saving mainly dependent on a reduction in indirect costs represents a further advantage in the use of iron carboxymaltose in this population.