Functional erythropoietin‐hepcidin axis in recombinant human erythropoietin independent haemodialysis patients

ABSTRACT Aim Relatively few haemodialysis (HD) patients remain independent of recombinant human erythropoietin (‘rHU‐EPO free patients’). We investigated the role of EPO and hepcidin, two key hormones involved in anaemia. Methods We report a monocentric case‐control series. Iron status, EPO and hepcidin levels were analysed in 15 Adult HD (Age > 18 years) with a stable haemoglobin (Hb) level that have not received rHU‐EPO for at least 6 months (=rHU‐EPO free patients); and in 60 controls with a stable rHU‐EPO dose and Hb level. Results The rHU‐EPO free patients had a higher Hb level compared to controls (12.1 ± 0.99 g/dL vs 11.1 ± 0.73, P = 0.0014), and a lower ferritin level (183 ± 102 vs 312 ± 166 ng/mL, P = 0.001). Hepcidin levels were lower in the rHU‐EPO free patients (12.53 ± 10.46 ng/mL) compared to the controls (37.95 ± 34.33 ng/mL), P = 0.0033. Hepcidin levels correlated significantly with ferritin levels; but neither with transferrin saturation, C‐reactive protein nor EPO levels. Unsupervised analysis revealed that rHU‐EPO free patients had a specific clinical/biological profile (presence of renal cyst, longer dialysis vintage, lower ferritin, and EPO and hepcidin levels compared to the control group). Finally, we showed that a lower ferritin level might be a surrogate marker of a lower hepcidin status in this population. Conclusion Recombinant human erythropoietin free patients seem to restore the EPO‐hepcidin axis that is critical for erythropoiesis. A specific combination of clinical and biological parameters may help to detect future rHU‐EPO free patients. Summary at a Glance This is a study of haemodialysis patients not receiving erythropoiesis‐stimulating agents (ESA), reporting lower hepcidin and ferritin levels as compared with ESA‐treated controls. The authors suggest a therapeutic relevance of these findings by showing progressive decreases in these parameters in the subgroup who were receiving erythropoietin (EPO), but became EPO‐independent afterwards.