- Design
- Prospective cohort study
- Population
- 3,826 adults with chronic kidney disease in the CRIC study
- Primary outcome
- Heart failure, kidney failure or halving of eGFR, and new diabetes by hepcidin tertile
- Effect
- Highest tertile: kidney outcome HR 1.19 (95% CI 1.09–1.30); atherosclerotic events HR 1.34
Hepcidin controls iron absorption and release, and rises with inflammation and falling kidney function. The Chronic Renal Insufficiency Cohort measured plasma hepcidin in 3,826 adults with CKD and followed cardiovascular, kidney and metabolic outcomes.
Higher hepcidin was associated with older age, diabetes, lower eGFR, more albuminuria, higher iron indices, FGF23 and inflammatory markers. Hepcidin was not linked to heart failure or new diabetes. Compared with the middle tertile, the highest tertile was associated with more kidney failure or halving of eGFR (HR 1.19, 95% CI 1.09–1.30) and more atherosclerotic events (HR 1.34, 95% CI 1.09–1.64). The lowest tertile was associated with higher all-cause and cardiovascular mortality, even after adjusting for iron and inflammation.
Hepcidin is not a routine test, and this does not support measuring it. It does reinforce that iron handling in CKD is not just about anaemia, and that both iron overload and deficiency states carry risk.
- Do not order hepcidin routinely; it is not a validated clinical test in CKD.
- Assess iron status with ferritin and transferrin saturation in CKD anaemia.
- Remember that inflammation raises ferritin and hepcidin and can mask iron deficiency.
- Avoid both iron deficiency and over-replacement when treating CKD anaemia.
Why it matters
A U-shaped link between hepcidin and outcomes suggests iron dysregulation in CKD harms in both directions.
Don't overread it
These associations from an observational cohort do not show that changing hepcidin changes outcomes.
The statistics, in plain English
Comparing the top and bottom thirds with the middle shows where risk rises. An HR of 1.34 means about a third higher rate of atherosclerotic events in the highest third, after adjustment — but adjustment cannot remove everything that travels with high hepcidin.
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