Narrative ReviewNew Treatment Approaches for the Anemia of CKD
Section snippets
Hypoxia-Inducible Factor Stabilizers
Hypoxia-inducible factors (HIFs) coordinate the physiologic response to systemic hypoxia by altering gene expression in certain cell types, leading to an increase in EPO production in the kidney and liver, improved uptake and use of iron, and changes to the bone marrow microenvironment that encourage erythroid progenitor maturation and proliferation.26
HIFs are heterodimers consisting of an oxygen-sensitive α subunit and a constitutively expressed β subunit. There are 3 HIF α subunits in
EPO Mimetic Peptides
EPO mimetic peptides (EMPs) are a group of synthetic cyclic peptides capable of stimulating the EPO receptor though their amino acid sequence is completely different from the hormone.85, 86 EMP-1, an oligopeptide containing 20 amino acids joined by a disulfide bridge between 2 cysteine residues, was synthesized in 1998.87 However, its short in vivo half-life and relatively weak binding to the EPO receptor hampered its clinical use.
In order to increase effectiveness, peptide dimers that use
Conclusions
The development of new strategies to treat anemia is still an evolving and fascinating area of experimental and clinical research. At present, the most promising class of agents seems to be HIF stabilizers, as evident in the number of molecules currently under development. This class of drug stimulates erythropoiesis by physiologic concentrations of endogenous EPO, which may translate into a clinical advantage because concerns for ESA safety are higher at the high doses. However, these
Acknowledgements
Support: None.
Financial Disclosure: Dr Del Vecchio has served on the advisory board of Astellas. Dr Locatelli has served on the advisory boards of Akebia, Amgen, Astellas, Fibrogen, Genzyme, GSK, Fresenius Medical Care, Janssen Cilag, Pharmacosmos, Keryx, and ZS Pharma and has been a speaker at a meeting supported by Amgen, Asahi Casei, Roche, and ZS Pharma. The remaining authors declare that they have no relevant financial interests.
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