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dc.contributor.authorMaxwell, Patricken
dc.contributor.authorEckardt, Kai-Uween
dc.date.accessioned2016-02-10T10:27:26Z
dc.date.available2016-02-10T10:27:26Z
dc.date.issued2015-12-14en
dc.identifier.issn1759-5061
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/253687
dc.description.abstractSmall-molecule stabilizers of hypoxia inducible factor (HIF) are being developed for the treatment of renal anaemia. These molecules inhibit prolyl hydroxylase domain-containing (PHD) enzymes, resulting in HIF activation and increased production of erythropoietin. Currently, renal anaemia is treated with recombinant human erythropoietin or related analogues, referred to as conventional erythropoiesis stimulating agents (ESAs). Advantages of PHD enzyme inhibitors over conventional ESAs include their oral administration and their simpler — and potentially cheaper — production. Importantly, inhibition of PHD enzymes is likely to have a range of consequences other than increasing levels of erythropoietin, and these effects could be beneficial — for instance by reducing the need for parenteral iron — but might in some instances be harmful. Several companies are currently testing PHD enzyme inhibitors in patients with renal anaemia and have reported clear evidence of efficacy without serious safety concerns. A central question that current studies are beginning to address is whether using PHD enzyme inhibitors will influence hard end points, including mortality and the rate of cardiovascular events. In terms of approaches to therapy, the exquisite specificity of conventional ESAs is a striking contrast to the pleiotropic effects of activating HIF. Excitingly, PHD inhibitors could also be useful for conditions besides renal anaemia, such as protection from ischaemic injury.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.subjectanaemiaen
dc.subjectchronic kidney diseaseen
dc.subjectdrug developmenten
dc.subjecterythropoietinen
dc.titleHIF prolyl hydroxylase inhibitors for the treatment of renal anaemia and beyonden
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrneph.2015.193en
prism.endingPage168
prism.publicationDate2015en
prism.publicationNameNature Reviews Nephrologyen
prism.startingPage157
prism.volume12en
rioxxterms.versionofrecord10.1038/nrneph.2015.193en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-12-14en
dc.contributor.orcidMaxwell, Patrick [0000-0002-0338-2679]
dc.identifier.eissn1759-507X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (096956/Z/11/Z)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0514-10122)
rioxxterms.freetoread.startdate2016-06-14


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