ESA, Iron Therapy and New Drugs: Are There New Perspectives in the Treatment of Anaemia?

Abstract

Anemia is a well-known consequence of chronic kidney disease (CKD); it is mainly due to a relative insufficiency of erythropoietin synthesis by the failing kidneys. Over the years, the combination of erythropoiesis stimulating agents (ESA) and iron has become the standard of care of anemia. All ESAs effectively increase hemoglobin (Hb) levels in a substantial percentage of patients. However, in the last decade, their use has been surrounded by safety issues in increased cardiovascular risk, especially when used at high doses in inflamed and hyporesponsive patients. This has led to the definition of a more cautious Hb target. Iron deficiency is very frequent in CKD patients, with a higher frequency in non-dialysis patients. Traditionally, iron supplementation is mostly used as supportive therapy for anemia control. However, the concept is growing that intravenous iron therapy per se could be beneficial in the presence of heart failure. A new class of drugs, prolyl hydroxylase domain (PHD) inhibitors (PHD inhibitors) is becoming available for the treatment of anemia in CKD patients. Theoretically, these agents have a number of advantages, the main ones being that of stimulating the synthesis of endogenous erythropoietin and increasing iron availability. The impact of their future use in clinical practice is still to be defined. Another possible strategy could be targeting serum hepcidin and its related pathways. This possibility is fascinating from the scientific point of view, but at present its development phase is still far from clinical application.