08/12/2025
🔑 Clinical Pearls: Anaemia Management in CKD (2025 Update)
1. Shift in Treatment Paradigm
The centre of gravity has shifted from
erythropoiesis-stimulating agents(ESAs)→ Iron-first strategies in recent years.
Adequate iron repletion often improves Hb enough to delay or avoid ESA initiation, especially in early CKD.
2. ESA Risks: Less is More
Targeting higher haemoglobin with ESAs increases stroke, venous thromboembolism, and cardiovascular events.
ESA doses should be minimal (just enough to avoid transfusion) and used only after correcting iron deficiency and other reversible causes.
3. High-Dose IV Iron Appears Safe & Beneficial
The PIVOTAL trial changed practice:
Monthly 400 mg IV iron sucrose, guided by cut-offs:
Ferritin ≤700 µg/L
TSAT ≤40%
Liberal IV iron reduces HF hospitalisation, possibly lowers MI risk, and improves ESA efficiency in dialysis patients.
4. HIF–PHIs: A New Era, With Caution
Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are orally active and stimulate endogenous EPO at physiological levels.
They also improve iron handling by upregulating iron-regulatory genes — useful in inflammatory ESA-resistant CKD.
5. Safety Concerns With HIF-PHIs
By activating broad HIF pathways, these agents may:
Increase VEGF, potentially worsening proliferative diabetic retinopathy.
Raise theoretical risks regarding tumour growth and progression.
Long-term safety data remain inadequate, so selection must be careful and individualized.
6. Iron Deficiency Remains the Cornerstone
In CKD with anemia, always rule out and treat iron deficiency first.
High hepcidin levels make oral iron poorly absorbed → consider IV iron early.
7. Multifactorial Nature of CKD Anaemia
Besides low EPO, remember contributors:
Iron deficiency (absolute or functional)
Inflammation
Reduced RBC lifespan
Dialysis-related blood loss
Correction of these improves response to ESAs and HIF-PHIs.
8. Practical Goal Setting
Aim for Hb 10–11 g/dL in most CKD patients.
Avoid pushing Hb >11.5 g/dL — no benefit, more harm.
9. Who Benefits Most From HIF-PHIs?
Patients with:
Poor response to ESAs
High inflammatory burden
Oral-therapy preference (non-dialysis CKD)
But avoid or use cautiously in active malignancy and diabetic retinopathy.
10. Key Takeaway for Clinicians
Iron optimization is the foundation; ESAs are the supplement; HIF-PHIs are the exciting but still-evaluated frontier
https://academic.oup.com/ndt/article/39/5/770/7452913?login=false
