{"id":"d1442dc3232f","type":"article","url":"https://hartvaat.nl/2026/08/18/hif-stabilisatoren-als-orale-alternatief-voor-esas-bij-anemie-bij-chronische-nie/","title":"HIF-stabilisatoren als orale alternatief voor ESAs bij anemie bij chronische nierziekte","title_en":"Beyond erythropoiesis-stimulating agents: The evolving role of hypoxia-inducible factor stabilizers in anemia of chronic kidney disease.","category":"chronische nierziekte","category_label":"Nierziekte","professions":["apotheker","cardioloog","internist"],"tags":[],"journal":"Clinical nephrology","doi":"10.5414/CN112100","source_url":"https://doi.org/10.5414/CN112100","authors":["Joel Shah","William Wells-Gatnik","Kunal Sharma","Sidhartha Senapati","Lakshmi Kattamuri","Aimee Hechanova","Fernanda Payan-Schober","Biff F Palmer"],"significance":6,"published":"2026-08-25","source_date":"2026-08-18","image":"","kennis":["https://hartvaat.nl/kennis/nierziekte/nierziekte-en-cardiovasculair-risico/","https://hartvaat.nl/kennis/nierziekte/nsaids-en-nierziekte/"],"congress":"","summary_en":"This narrative review evaluates hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) as an oral treatment for anemia in chronic kidney disease (CKD). Phase 3 trials demonstrate that HIF-PHIs are non-inferior to erythropoiesis-stimulating agents (ESAs) and effectively maintain hemoglobin levels, while also improving iron mobilization by lowering hepcidin. However, emerging safety signals regarding major adverse cardiovascular events and thromboembolism, particularly in non-dialysis patients, have prompted divergent regulatory approvals across regions. Clinicians should consider HIF-PHIs a promising alternative to ESAs, but therapy initiation requires individualized cardiovascular risk assessment and ongoing post-marketing surveillance.","created":"2026-08-19T00:51:16Z","updated":"2026-08-19T00:51:16Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Deze narratieve review evalueert de rol van HIF-stabilisatoren (HIF-PHIs) bij anemie bij patiënten met chronische nierziekte (CKD). Fase-3-trials tonen aan dat deze orale middelen niet-inferieur zijn aan erytropoëtine-stimulerende agentia (ESAs) en de hemoglobinespiegel effectief verhogen, terwijl ze tevens de ijzermobilisatie verbeteren door hepcidine te verlagen. Echter, signalen over verhoogde thromboembolische en cardiovasculaire risico’s, vooral bij niet-dialysepatiënten, leiden tot verschillende regelgeving in de VS versus Europa. Voor de klinische praktijk betekent dit dat HIF-PHIs een waardevol alternatief zijn, maar de start vereist een zorgvuldige afweging van individuele risico’s en nauwgezette opvolging.","abstract_original":"Anemia is one of the most common complications affecting individuals with chronic kidney disease (CKD). It is driven primarily by relative erythropoietin (EPO) deficiency, chronic inflammation, and altered iron metabolism. Emerging therapies, known as hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), offer a novel oral treatment approach by stabilizing intracellular HIF levels to mimic tissue hypoxia and stimulate endogenous EPO production. This comprehensive narrative review synthesizes literature indexed in PubMed, MEDLINE, Scopus, and Web of Science to evaluate the efficacy of HIF stabilizers in the anemia of CKD compared to current guideline-directed therapies worldwide. Phase 3 clinical trials consistently demonstrate that HIF-PHIs are non-inferior to conventional erythropoiesis-stimulating agents (ESAs) and superior to placebo in increasing and maintaining hemoglobin levels in both dialysis-dependent and non-dialysis-dependent CKD patients. Additionally, HIF-PHIs improve iron mobilization and utilization by decreasing hepcidin levels. However, trials have raised safety concerns regarding cardiovascular outcomes, including major adverse cardiovascular events, and an increased incidence of thromboembolic events, particularly in non-dialysis-dependent populations. These safety signals have led to divergent global regulatory pathways, with the United States Food and Drug Administration largely restricting approvals to dialysis-dependent patients, while agencies in Europe and Japan have granted broader authorizations. As a growing body of literature accumulates, HIF-PHIs offer a promising oral alternative to ESAs that addresses both relative EPO deficiency and iron sequestration. While they have the potential to become a new standard of care, therapy initiation requires individualized risk-benefit assessments, and continued post-marketing surveillance is necessary to fully elucidate long-term cardiovascular and thromboembolic risks."}