Abstract
Hepcidin is a small peptide with a critical role in cellular iron homeostasis, as it regulates utilization of stored iron and antimicrobial defense in inflammation (bacterial and fungal). Since it was isolated in 2000, and especially in the last decade, numerous studies aimed to evaluate the clinical use of plasma and urine hepcidin as a marker of anemia, especially anemia of chronic disease and post-transplant anemia (PTA). Hepcidin regulation is delicately tuned by two inflammatory pathways activated by interleukin-6 (IL-6) and bone morphogenic proteins (BMPs) and iron regulated pathway sensitive to circulating transferin-iron (TR-Fe) complex. BMP-mediated pathway and TR-Fe sensitive pathway seem to be connected by hemojuveline, a BMP co-factor that interacts with transferine receptor 2 (TRF2) in cases of high TR-Fe circulatory concentration. In addition to these regulatory mechanisms other regulators and signaling pathways are being extensively researched. Hepcidin has been identified as an important contributor to morbidity and mortality in end stage renal disease (ESRD) but no such association has jet been found in case of PTA. However, there is an association between higher doses of erythropoiesis-stimulating agents (ESA) and mortality in the posttransplant period and the assumption that hepcidin might play a role in ESA resistance in PTA. Thus the review’s main goal was to summarize papers published on the association of hepcidin with PTA, give up-to-date information on hepcidin regulation and on potential therapeutics that optimize hepcidin regulation. We also compared the performances of tests for hepcidin determination and reviewed research on immunosuppressants’ (IS) effect on hepcidin concentration.
Highlights
We reviewed all studies accessed by literature search of PubMed and SCOPUS from January 2000 to January 2015
The terms used as key words for the search were “hepcidin kidney transplantation” and “hepcidin post-transplant anemia”
Based exclusively on hepcidin results, the authors suggested that sirolimus interferes with iron metabolism and that in this case post-transplant anemia (PTA) does not present the features of inflammation-related anemia, since serum hepcidin was similar in the two groups after therapy randomization
Summary
We reviewed all studies accessed by literature search of PubMed and SCOPUS from January 2000 to January 2015. It was found to be essential for HJV function in mice, but this is still to be confirmed in humans [14] Another hepcidin up-regulating mechanism appears to be activated by endoplasmatic reticulum stress, which activates hepcidin promoter gene through the cyclic adenosine monophosphate (cAMP) response elementbinding protein H (CREBH), a liver-specific transcription factor [15]. A study performed on freshly isolated mice hepatocytes and human hepatocytes (cell line HepG2) showed that hepcidin mRNA was down-regulated by EPO, administered in supraphysiological, therapeutic doses, in a dose-dependent manner This effect was blocked by anti-EPO receptor (anti-EPO-R) antibody, along with a down-regulation of CCAAT/ enhancer-binding protein α gene (CEBPA gene) mRNA that is responsible for expression of signaling protein C/EBPα (CCAAT/enhancer-binding protein α).
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