Iron deficiency anemia is a common and clinically important concern in patients with CKD. In this patient population, chronic inflammation may lead to increased hepcidin production, in turn inhibiting both the uptake of dietary iron and the mobilization of stored iron from the reticuloendothelial system to circulating transferrin.

The problem is exacerbated in patients receiving dialysis who experience significant additional iron losses due to blood remaining in the dialyser circuit after treatment. Patients with CKD receiving treatment with erythropoiesis-stimulating agents (ESAs) are very prone to iron deficiency due to the increased demand for iron to support erythropoiesis, and indeed iron deficiency is the most commonly identified cause of hyporesponsiveness to ESA therapy in dialysis patients. As a result, iron therapy, either alone or in combination with ESA treatment, has been an important component of the management of anemia in patients with CKD for many years.

Until now, the concern has been that high-dose intravenous (IV) iron would increase the risk of infection in a dialysis population already heavily predisposed to infection, as previous observational studies have shown.

There are adverse safety signals associated with the use of higher doses of the erythropoietins, including increased vascular access thrombosis, increased CV events and increased risk of cancer and recurrent cancers.

Recently, the PIVOTAL study suggested that the proactive use of high-dose IV iron can reduce the amount of ESA needed to treat anemia in dialysis patients with no short-term increase in the risk for vascular complications or infections. With the higher dose of IV iron, the investigators used less ESA and, in using less ESA, we may, in the longer-term, be protecting our patients from the CV risk associated with higher ESA doses.