Hepcidin, a cysteine-rich polypeptide mainly produced by hepatocytes, might serve as a biomarker of resistance/hyporesponsiveness to erythropoiesis-stimulating agents (ESA) in patients on hemodialysis (HD), according to researchers.  

In a study of 60 HD patients from Ain Shams University in Cairo matched to 30 healthy controls, HD patients displayed higher hepcidin, interleukin 6 (IL-6), and high sensitivity C reactive protein (hs CRP) levels and lower hemoglobin (Hb) values.

“These results probably represent the inflammatory nature of the disease as well as the decreased iron absorption and mobilization in HD patients,” a team led by Botheina A. Farweez, MD, explained in International Urology and Nephrology. The findings concur with those of several previous studies.

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Dr Farweez and colleagues further examined HD patients according to their response to ESA therapy. Non-responders had higher hepcidin, IL-6, and hsCRP levels, a higher erythropoietin resistance index (ERI), and a lower Hb level. Hepcidin likewise correlated with the inflammatory markers but was inversely related to Hb. According to a receiver operating characteristic curve analysis, cut-offs of 280 ng/mL or higher for hepcidin and 7.5 or more for ERI differentiated responders from non-responders with a prognostic accuracy of 83% and 77.3%, respectively. Hepcidin significantly increased with increasing tertiles of ERI.

“Hepcidin leads to the decreased activation of ferroportin in enterocytes, hepatocytes and macrophages, causing decreased iron absorption and release,” Dr Farweez’s team stated. “Because of the relationships among inflammation, hepcidin and ESA resistance/hyporesponsiveness, it may be hypothesized that hepcidin has potential as a marker of ESA resistance/hyporesponsiveness in CKD patients and could serve an important marker for predicting the response to ESA treatment.”

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El Sewefy DA, Farweez BA, Behairy MA, and Yassin NR. Impact of serum hepcidin and inflammatory markers on resistance to erythropoiesis-stimulating therapy in haemodialysis patients. Intl Urol Nephrol. DOI:10.1007/s11255-018-2062-z