Recombinant human erythropoietin (epoetin) has been available for the treatment 
of renal anemia for more than 20 years, and within the last decade two 
molecularly engineered analogues darbepoetin alfa and pegylated epoetin beta 
were introduced as longer-acting erythropoiesis-stimulating agents. Recently, 
newer strategies for correcting anemia have been explored, some of which remain 
in the laboratory while others are translating across into clinical trials. 
Peginesatide has completed phase 3 clinical trials for the treatment of anemia 
associated with chronic kidney disease; this molecule is immunologically 
distinct from the erythropoietic proteins, with no cross-reactivity with 
anti-erythropoietin antibodies. HIF (hypoxia inducible factor) stabilization 
involves the pharmacologic inhibition of prolyl hydroxylation of HIF-α (the 
major transcription factor controlling erythropoietin gene expression), thereby 
preventing its degradation in the proteasome. Hepcidin is the master regulator 
of iron metabolism, and this peptide is upregulated in inflammatory conditions, 
including uremia; its antagonism has been shown to cause amelioration of 
inflammatory anemia in animal models. For the time being, 
erythropoiesis-stimulating agent therapy remains the mainstay of anemia 
management in chronic kidney disease, but it is possible that one or more of the 
strategies discussed in this review may have a future role in the treatment of 
this condition.