Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Aug;92(2):306-312.
doi: 10.1016/j.kint.2017.02.035. Epub 2017 Jun 24.

Prolyl hydroxylase domain inhibitors as a novel therapeutic approach against anemia in chronic kidney disease

Mai Sugahara  1 , Tetsuhiro Tanaka  1 , Masaomi Nangaku  2
Affiliations
Free article
Review

Prolyl hydroxylase domain inhibitors as a novel therapeutic approach against anemia in chronic kidney disease

Mai Sugahara et al. Kidney Int. 2017 Aug.
Free article

Abstract

Anemia is a common complication of chronic kidney disease and is mainly caused by the inability of injured kidneys to produce adequate amounts of erythropoietin. Studies elucidating the regulation of erythropoietin production led to the identification of hypoxia-inducible factor (HIF), which activates the transcription of genes that mediate adaptive responses to hypoxia. HIF is a heterodimer that consists of an α and β subunit. While HIF-β is constitutively expressed, HIF-α is subjected to ubiquitination and proteasomal degradation under normoxic conditions. This process is mediated by prolyl hydroxylase domain proteins, the inhibition of which results in an increased expression of hypoxia-induced genes, including erythropoietin. These findings led to the development of prolyl hydroxylase domain inhibitors as novel therapeutic agents against anemia in chronic kidney disease. Prolyl hydroxylase domain inhibition improves iron metabolism, which also contributes to erythropoiesis. To date, at least 6 small-molecule inhibitors of the prolyl hydroxylase domain have been tested in humans, and clinical trials have shown that they are effective without causing serious adverse events. However, there is a theoretical concern that the systemic activation of HIF could also induce deleterious effects such as tumorigenesis and severe pulmonary hypertension, which demands careful assessments in future clinical studies.

Keywords: anemia; erythropoietin; hypoxia-inducible factor; prolyl hydroxylase domain.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

  NODES
INTERN 1
twitter 2