skip to main content

HIF-PHI Mechanism PHD Inhibition EPO Iron — ESENeph MCQ

Instant feedback + full explanation. One question, done properly.

ModerateChronic Kidney DiseaseHIF-PHI Mechanism PHD Inhibition EPO IronESENeph

A 68-year-old man with CKD G5D on haemodialysis has just been started on a HIF-PHI (roxadustat) for anaemia after ESA hyporesponsiveness. Which mechanism distinguishes HIF-PHIs from conventional ESAs?

Educational content. Not a substitute for clinical judgement or local policy.

Reveal the answer and explanation

Correct answer: C — HIF-PHIs inhibit prolyl hydroxylase, stabilising HIF-alpha to stimulate endogenous EPO production and improve iron utilisation

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors (HIF-PHIs, e.g., roxadustat, daprodustat, vadadustat) represent a novel mechanism for anaemia management in CKD. They inhibit prolyl hydroxylase domain enzymes (PHD1-3), preventing HIF-alpha degradation. Stabilised HIF-alpha translocates to the nucleus, binding HIF-beta and activating transcription of EPO (increasing endogenous EPO production) and iron metabolism genes (suppressing hepcidin, increasing ferroportin expression, enhancing iron absorption and mobilisation). This dual action — EPO stimulation plus improved iron utilisation — distinguishes them from ESAs, which only stimulate the EPO receptor. HIF-PHIs are oral agents, offering convenience. Safety considerations include potential effects on angiogenesis and tumour growth.

Reference: KDIGO 2025 – Anaemia in CKD; Chen et al 2019 – Roxadustat Phase 3