Anemia in chronic kidney disease patients: treatment recommendations and emerging therapies

Abstract

Erythropoiesis-stimulating agents (ESA) and iron have been available since decades to treat anemia of chronic kidney disease (CKD). However, many grey areas surround the field. The optimal hemoglobin (Hb) target to aimed at with ESA, the general safety of ESA and boundaries to not be exceeded with iron supplementation are still to be clearly defined. New strategies to stimulate erythropoiesis and new iron molecules have been developed; the most promising approach is the manipulation of the hypoxia-inducible transcription factor (HIF) system. The regulation of activin A pathway is another option with good potential, also considering the additional advantage of increasing bone mass. New iron molecule for intravenous administration may be useful to reduce the number of doses to be administered.

Keywords::

• activin
• anemia
• chronic kidney disease
• erythropoiesis
• erythropoietin
• hemoglobin
• prolyl hydroxylase inhibitor

Financial & competing interests disclosure

F Locatelli has been member of advisory boards or speaker at meetings supported by Abbvie, Amgen, Farmacosmos, Fibrogen, Janssen, GSK, Hospira, Keryx, MCI, Roche, Rockwell Medical, Shire, Takeda, Vifor-Fresenius Pharma. L Del Vecchio has been speaker at meetings supported by Janssen and Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Hemoglobin normalization with erythropoiesis-stimulating agents is not effective and can even be harmful.

• International Societies/Organisations have given different suggestion about anemia management in chronic kidney disease patients.

• There is wide consensus in not intentionally exceeding with erythropoiesis-stimulating agents hemoglobin values of 13 g/dl and being cautious in patients with high cardiovascular risk and previous history of stroke and malignancies.

• Treatment indications to iron therapy have been broadened following the publication of the Trial to Reduce Cardiovascular Events with Aranesp^® Therapy study.

• New iron molecules for intravenous administration may be useful in the clinical setting, reducing the number of dose administrations and the workload for facilities.

• Iron-containing phosphate binders have the potential of reducing the need for intravenous iron administration.

• Prolyl hydroxylase inhibitors induce hypoxia-inducible transcription factors activity that stimulates the synthesis of endogenous erythropoietin and improve mobilization of iron stores. These agents can be given orally.

• Sotatercept is a dimeric fusion protein that binds to activin, preventing activin from binding endogenous receptors and interfering with downstream signaling cascades, in particular the SMAD2/3 pathway. It can increase both bone mass and hematocrit levels.