Hypoxia-inducible factor prolyl hydroxylase inhibitors for anaemia in chronic kidney disease: a clinical practice document by the European Renal Best Practice board of the European Renal Association

Anaemia is a common complication of chronic kidney disease (CKD) and is associated with poor long-term outcomes and quality of life. The use of supplemental iron, erythropoiesis-stimulating agents (ESAs) and blood transfusions has been the mainstay for treatment of anaemia in CKD for more than 3 dec...

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Bibliographic Details
Authors: Stoumpos, Sokratis, Crowe, Kirsty, Sarafidis, Pantelis, Barratt, Jonathan, Bolignano, Davide, Vecchio, Lucia Del, Małyszko, Jolanta, Więcek, Andrzej, Ortiz Arduán, Alberto, Cozzolino, Mario
Format: article
Publication Date:2024
Country:España
Institution:Universidad Autónoma de Madrid
Repository:Biblos-e Archivo. Repositorio Institucional de la UAM
Language:English
OAI Identifier:oai:repositorio.uam.es:10486/720769
Online Access:http://hdl.handle.net/10486/720769
https://dx.doi.org/10.1093/ndt/gfae075
Access Level:Open access
Keyword:anaemia
chronic kidney disease
erythropoiesis-stimulating agents
erythropoietin
hypoxia-inducible factor prolyl hydroxylase inhibitors
Medicina
Description
Summary:Anaemia is a common complication of chronic kidney disease (CKD) and is associated with poor long-term outcomes and quality of life. The use of supplemental iron, erythropoiesis-stimulating agents (ESAs) and blood transfusions has been the mainstay for treatment of anaemia in CKD for more than 3 decades. Despite available treatments, CKD patients with anaemia are undertreated and moderate–severe anaemia remains prevalent in the CKD population. Anaemia has consistently been associated with greater mortality, hospitalization, cardiovascular events and CKD progression in CKD patients, and the risk increases with anaemia severity. Hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitors have a novel mechanism of action by mimicking the body’s response to hypoxia and have emerged as an alternative to ESAs for treatment of anaemia in CKD. Their efficacy in correcting and maintaining haemoglobin has been demonstrated in >30 phase 3 clinical trials. Additionally, HIF activation results in various pleiotropic effects beyond erythropoiesis, with cholesterol reduction and improved iron homeostasis and potential anti-inflammatory effects. The long-term safety of these agents, particularly with respect to cardiovascular and thromboembolic events, and their possible effect on tumour growth needs to be fully elucidated. This article presents in detail the effects of HIF-PH inhibitors, describes their mechanisms of action and pharmacologic properties and discusses their place in the treatment of anaemia in CKD according to the available evidence