Abstract

Recombinant human erythropoietin (rHuEPO) has revolutionized the management of anemia in patients with chronic kidney disease. However, being similar to the naturally occurring molecule, rHuEPO is not a perfect pharmaceutical. Given its relatively short halflife, it requires a relatively frequent administration schedule. Moreover, it can be administered only subcutaneously or intravenously and it is unstable at room temperature, making necessary a strict cold chain. Pharmacological research has focused on the development of new agents in order to circumvent these relative disadvantages. New-generation erythropoietin-stimulating agents containing increased carbohydrate content (i.e. darbepoetin-alpha) or a large water-soluble polyethylene glycol moiety (continuous erythropoiesis receptor activator) are already available or nearly for clinical use and allow less frequent administration schedules than rHuEPO. Hematide, which is a dimeric peptide with chemical structure unrelated to EPO, is undergoing phase III clinical trials. Other possible strategies currently under research include fusion EPO proteins, gene therapy, hypoxia-inducible transcription factor stabilizers, GATA inhibition and hematopoietic cell phosphatase inhibition.