Role of Prohepcidin, Inflammatory Markers and Iron Status in Resistance to rhEPO Therapy in Hemodialysis Patients

• Published in: American journal of nephrology Vol. 28; no. 4; pp. 677 - 683
• Main Authors: Costa, Elísio, Pereira, Brian J.G., Rocha-Pereira, Petronila, Rocha, Susana, Reis, Flávio, Castro, Elisabeth, Teixeira, Frederico, Miranda, Vasco, do Sameiro Faria, Maria, Loureiro, Alfredo, Quintanilha, Alexandre, Belo, Luís, Santos-Silva, Alice
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2008
• Subjects: Antimicrobial Cationic Peptides - analysis; Antimicrobial Cationic Peptides - physiology; Biomarkers - blood; Blood Cell Count; C-Reactive Protein - analysis; Drug Resistance - physiology; Erythropoietin - therapeutic use; Female; Ferritins - blood; Hepcidins; Humans; Iron - blood; Male; Middle Aged; Original Report: Patient-Oriented, Translational Research; Protein Precursors - analysis; Protein Precursors - physiology; Receptors, Interleukin-3 - blood; Recombinant Proteins; Renal Dialysis; Reticulocytes - cytology; Transferrin - analysis; Resistance; Iron metabolism; Erythropoietin; Prohepcidin; rhEPO; Iron; Hepcidin
• ISSN: 0250-8095; 1421-9670
• DOI: 10.1159/000121478

The aim of our study was to assess possible relations between prohepcidin, iron status and inflammatory markers in hemodialysis (HD) patients, as well as its association with resistance to recombinant human erythropoietin (rhEPO) therapy. Fifty HD patients and 25 healthy controls were enrolled in the study. Among HD patients, 25 were non-responders and 25 were responders to rhEPO therapy. Complete blood cell count, reticulocyte count, and circulating levels of ferritin, iron, transferrin saturation, C-reactive protein (CRP), soluble interleukin (IL)-2 receptor (s-IL2R), soluble transferrin receptor (s-TfR), IL-6 and prohepcidin were measured in all patients and controls. HD patients showed higher circulating levels of ferritin, s-TfR, CRP, IL-6, s-IL2R and prohepcidin, and lower levels of transferrin compared to healthy controls. Higher levels of s-TfR, CRP and lower levels prohepcidin were observed among non-responders compared to responders. Prohepcidin levels correlated negatively with s-TfR and reticulocyte count. The weekly rhEPO/kg dose was found to be positively correlated with CRP, hemoglobin and s-TfR. In conclusion, our data show that a close interaction exists between inflammation, iron status and prohepcidin serum levels that ultimately regulate intracellular iron availability. Prohepcidin and s-TfR, together with CRP, may prove to be good markers of resistance to rhEPO therapy in HD patients.