Volume 30, Issue 168, February 2026

Roxadustat – a representative of hypoxia-inducible factor prolyl hydroxylase inhibitors: mechanism of action, safety, and efficacy

Michał Borowski^1♦, Julia Aleksandra Leśniak², Natalia Maria Leśniak³, Klaudia Martyna Patrzykąt⁴, Anna Maria Zakrzewska⁵, Kinga Popielarska⁶, Klaudia Elżbieta Niwińska⁷, Julia Agnieszka Michalak⁸, Aleksander Midera⁹, Monika Augustyn¹⁰

¹SPZOZ (Independent Public Healthcare Center) Mińsk Mazowiecki, Szpitalna St. 37, 05-300 Mińsk Mazowiecki, Poland
²Central Clinical Hospital of the Medical University of Łódź, 251 Pomorska Street, 92-213 Łódź, Poland
³Central Clinical Hospital of the Medical University of Łódź, 251 Pomorska Street, 92-213 Łódź, Poland
⁴109 Military Hospital with Policlinic in Szczecin, St. Piotra Skargi 9- 11, 70-965 Szczecin, Poland
⁵Central Clinical Hospital of the Medical University of Łódź, 251 Pomorska Street, 92-213 Łódź, Poland
⁶Medical University of Gdańsk, Marii Skłodowskiej-Curie 3a Street, 80-210 Gdańsk, Poland
⁷Prof. W. Orłowski Independent Public Clinical Hospital, CMKP, 231 Czerniakowska Street 00-416 Warsaw, Poland
⁸Poznan University of Medical Science SPZOZ (Independent Public Healthcare Center) Kościan u. Szpitalna 7, 64-000 Kościan; Poland
⁹SPZOZ (Independent Public Healthcare Center) Brzeziny, Tulipanowa St. 8, 95-060: Brzeziny, Poland
¹⁰Wroclaw Medical University, 1 Ludwik Pasteur, 50-367 Wrocław, Poland

^♦Corresponding author
Michał Borowski, SPZOZ (Independent Public Healthcare Center) Mińsk Mazowiecki, Szpitalna St. 37, 05-300 Mińsk Mazowiecki, Poland

ABSTRACT

Roxadustat is one of several representatives of a new group of drugs known as HIFPH inhibitors. It is attempting to gain recognition in medicine, mainly in the treatment of anemia in the course of CKD chronic kidney disease. Still, it may also prove effective in anemic patients with other diseases: MDS (myelodysplastic syndrome), PRCA (pure red cell anemia), or CIA (chronic inflammation anemia) such as RA, SLE, UC. This study aims to present the mechanism of action of roxadustat and its impact on hemoglobin levels. It also aims to compare the effectiveness of roxadustat with that of existing therapies for anemia in patients with CKD (Chronic Kidney Disease) and CIA (Chronic Inflammatory Anemia). A review of the scientific literature related on the use of roxadustat in patients with various stages of CKD and in other diseases such as MDS was conducted. Like ESA, roxadustat, induces an increase in RBC count. However, unlike ESA, which are EPO receptor agonists, roxadustat stimulates endogenous EPO production. This allows it to be more effective in achieving and maintaining Hb levels of 11 ± 1g/dL in inflammatory conditions. It achieves this by inhibiting HIF-PH, thereby increasing the cell's ability to survive in hypoxia conditions and enhancing its antioxidant potential. However, due to its polygenic action, it also affects other gene pathways. Further research is needed to understand the full spectrum of the drug. However, both China and the EMA decided to approve the drug for marketing, while the FDA rejected it.

Keywords: Roxadustat, HIF-PH inhibitor, ESA, Chronic kidney disease, Anemia, Chronic Inflammation Anemia (CIA)

Medical Science, 2026, 30, e39ms3797

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DOI: https://doi.org/10.54905/disssi.v30i168.e39ms3797

Published: 23 February 2026