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Roxadustat HIF-PHI Mechanism — ESENeph MCQ

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ModerateChronic Kidney DiseaseRoxadustat HIF-PHI MechanismESENeph

A 62-year-old man with CKD G4 (eGFR 22) and type 2 diabetes has anaemia (Hb 88 g/L) with adequate iron stores. His nephrologist discusses starting Roxadustat instead of a traditional ESA. What is Roxadustat's mechanism of action?

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Correct answer: E — Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) – stimulates endogenous EPO production and improves iron utilisation

Roxadustat is an oral HIF-PHI that inhibits prolyl hydroxylase, stabilising HIF-alpha. This mimics the physiological hypoxia response, increasing endogenous erythropoietin production and enhancing iron absorption and mobilisation. KDIGO 2025 anemia guideline includes HIF-PHIs as an option for anaemia management in CKD. Advantages include oral administration and improved iron utilisation. Concerns include potential VEGF-mediated effects, thrombosis risk, and tumour growth promotion. Long-term safety data is still accumulating.

Reference: KDIGO 2025 – Anemia in CKD; NICE TA920 2023 – Roxadustat